Antinutritional properties of plant lectins
Ilka M. Vasconcelos*, Jose
´Tadeu A. Oliveira
Departamento de Bioquı
´mica e Biologia Molecular, Universidade Federal do Ceara
´, Caixa Postal 6020,
Campus do Pici, CEP 60451-970, Fortaleza, CE, Brazil
Available online 2 June 2004
Lectins are carbohydrate binding (glyco)proteins which are ubiquitous in nature. In plants, they are distributed in various
families and hence ingested daily in appreciable amounts by both humans and animals. One of the most nutritionally important
features of plant lectins is their ability to survive digestion by the gastrointestinal tract of consumers. This allows the lectins to
bind to membrane glycosyl groups of the cells lining the digestive tract. As a result of this interaction a series of harmful local
and systemic reactions are triggered placing this class of molecules as antinutritive and/or toxic substances. Locally, they can
affect the turnover and loss of gut epithelial cells, damage the luminal membranes of the epithelium, interfere with nutrient
digestion and absorption, stimulate shifts in the bacterial ﬂora and modulate the immune state of the digestive tract.
Systemically, they can disrupt lipid, carbohydrate and protein metabolism, promote enlargement and/or atrophy of key internal
organs and tissues and alter the hormonal and immunological status. At high intakes, lectins can seriously threaten the growth
and health of consuming animals. They are also detrimental to numerous insect pests of crop plants although less is presently
known about their insecticidal mechanisms of action. This current review surveys the recent knowledge on the
antinutritional/toxic effects of plant lectins on higher animals and insects.
q2004 Elsevier Ltd. All rights reserved.
Keywords: Plant lectins; Antinutritional effects; Higher animals; Insects
1. Introduction ................................................................... 385
2. Lectins in plant foods ............................................................ 386
3. Oral toxicity of plant lectins to higher animals.......................................... 387
4. Resistance of lectins to proteolysis .................................................. 388
5. Effects of lectins on the digestive tract ............................................... 389
6. Systemic effects of dietary lectins ................................................... 390
7. Insecticidal properties of plant lectins ................................................ 393
8. Conclusions ................................................................... 397
References ....................................................................... 397
Plant lectins were originally detected by the medical
student Stillmark (1888), in Dorpat/Estonia when he was
working on his dissertation thesis on castor beans (Ricinus
communis L.). At this time he described the presence of a
toxic proteinaceous factor in extracts from castor beans
which also agglutinated red blood cells. To indicate the
source in which it had been found the name ricin was
adopted. Thus, historically, this fact is considered the true
starting point of the research on plant lectins (Ru
1998). The term lectin (legere ¼Latin verb for to select)
was coined by Boyd many years later to emphasise the
ability of some hemagglutinins to discriminate blood cells
within the ABO blood group system (Boyd and Reguera,
1949; Boyd and Shapleigh, 1954). Presently, the term lectin
is prevalent over that of hemagglutinin and is broadly
0041-0101/$ - see front matter q2004 Elsevier Ltd. All rights reserved.
Toxicon 44 (2004) 385–403
*Corresponding author. Fax: þ55-85-288-9789.
E-mail address: firstname.lastname@example.org (I.M. Vasconcelos).
employed to denote ‘all plant proteins possessing at least
one non-catalytic domain, which binds reversibly to a
speciﬁc mono- or oligosaccharide’ (Peumans and Van
Damme, 1995). Alternatively, lectins are also deﬁned as
‘proteins or glycoproteins of non-immune origin with one or
more binding sites per subunit, which can reversibly bind to
speciﬁc sugar segments through hydrogen bonds and
Van Der Waals interactions’ (Lis and Sharon, 1998). Both
these deﬁnitions are very comprehensive and include non-
agglutinating and some enzyme proteins (Van Damme et al.,
1998) such as the class I plant chitinase, considered as a
lectin because its single carbohydrate-binding domain is
structurally distinct of its catalytic site and does not directly
participate in the chitinolytic activity of this enzyme
(Peumans and Van Damme, 1994). Obviously, chitinases
cannot be called as agglutinins or phytohemagglutinins
since they do not possess agglutination and/or glycoconju-
gate precipitation properties, as they are not multivalent
carbohydrate-binding proteins. Another class of plant
proteins which are also considered as lectins, according to
the above deﬁnitions, are the type 2 RIPs (ribosome-
inactivating proteins). Ricin, abrin and modeccin are well
known examples of two-chain RIPs which irreversibly
inactivate ribosomes by removing a speciﬁc adenine from a
highly conserved tetranucleotide‘GA
GA’loop present in
28 S RNA of the large ribosomal subunit (Endo and Tsurugi,
1987; Barbieri et al., 1993). The high toxicity of these
proteins to living cells is associated to the A chain which
possesses the enzymatic RNA-N-glycosidase domain but it
is the carbohydrate-binding or lectin domain in the B chain
which interacts with cell surface sugar receptors, mediating
endocytosis of type 2 RIPs, an essential event that precedes
cellular toxicity (Barbieri et al., 1993; Peumans and Van
Damme, 1994; Olsnes et al., 1999).
Considering the overall structure of plant lectins they are
subdivided into four major classes: Merolectins which are
proteins having a single carbohydrate-binding domain;
Hololectins, comprising all lectins having di- or multivalent
carbohydrate-binding sites; Chimerolectins, proteins con-
sisting of one or more carbohydrate-binding domain(s) plus
an additional catalytic or another biological activity
dependent on a distinct domain other than the carbo-
hydrate-binding site; and Superlectins which also possess at
least two carbohydrate-binding domains but differ from the
hololectins because their sites are able to recognise
structurally unrelated sugars (Van Damme et al., 1998).
Although plant lectins are considered a very complex and
heterogeneous group of proteins at the biochemical/
physicochemical viewpoint, sequence, structural infor-
mation and molecular cloning of lectin genes enable
subdivision of plant lectins in seven families of structurally
and evolutionary related proteins: legume lectins; chitin-
binding lectins; type 2 RIP and related lectins; monocot
mannose-binding lectins; jacalin-related lectins; amaranthin
lectin family and cucurbit phloem lectins (reviewed in Van
Damme et al., 1998; Murdock and Shade, 2002).
Plant lectins are also subdivided into ﬁve groups, according
to the monosaccharide for which they exhibit the highest
afﬁnity: D-mannose/D-glucose, D-galactose/N-acetyl-D-
galactosamine, N-acetyl-D-glucosamine, L-fucose and N-
acetylneuraminic acid (Goldstein et al., 1997). Thus
depending on the speciﬁcity toward a given monosaccharide
the lectin will selectively bind to one of these above sugars
which are typical constituents of eukaryotic cell surfaces
(Lis and Sharon, 1998). In regard to their localisation, plant
lectins are generally most abundant in the seeds but they are
also found in different vegetative tissues such as in roots,
leaves, barks, ﬂowers, bulbs and rhizomes (Broekaert et al.,
1987; Peumans et al., 1997; Ratanapo et al., 1998; Van
Damme et al., 2000).
The wide distribution of lectins in all tissues of plants
and their ubiquitous presence in the plant kingdom suggest
important roles for these proteins. One possible physiologi-
cal function that has emerged is the defensive role of these
carbohydrate-binding proteins against phytopathogenic
microorganisms, phytophagous insects and plant-eating
animals (Chrispeels and Raikhel, 1991; Harper et al.,
1995; Gatehouse et al., 1995). Indeed it has been shown
that plant lectins possess cytotoxic, fungitoxic, anti-insect
and anti-nematode properties either in vitro or in vivo and
are toxic to higher animals (Oliveira et al., 1994; Peumans
and Van Damme, 1995; Oka et al., 1997; Ripoll et al., 2003).
For example, the toxic effects of PHA, the lectin from
Phaseolus vulgaris, on monogastric animals are well
documented (Pusztai, 1991; Pusztai et al., 1995), and the
expression in transgenic plants of genes encoding for the
lectins GNA (from Galanthus nivalis; snowdrop), PSA
(Pisum sativum; pea), WGA (Triticum vulgare; wheatgerm),
ConA (Canavalia ensiformis; jack bean), AIA (Artocarpus
integrifolia; jack fruit), OSA (Oriza sativa; rice) and UDA
(Urtica dioica; stinging nettle) resulted in added protection
against insect pests and/or phytopathogenic nematodes or
fungi (Hilder et al., 1995; Does et al., 1999; Hilder and
Boulter, 1999; Powell, 2001; Ripoll et al., 2003).
One of the most important features of plant lectins,
compatible with the proposed defensive function, is the
remarkably high resistance to proteolysis and stability over
a large range of pH, even when they are out of their natural
2. Lectins in plant foods
Plants offer an enormous variety of macro- and
micronutrients necessary for heterotrophs such as microbes
and plant-eating organisms including nematodes, insects,
various other invertebrates and higher animals. Food for
human consumption is derived either from plant sources or
from animals. Animals themselves are ultimately dependent
upon plants for their survival. As lectins are present in the
most commonly edible plant foods such as tomato, potato,
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403386
beans, peas, carrots, soybeans, cherries, blackberries, wheat
germ, rice, corn, garlic, peanuts, mushrooms, avocado,
beetroot, leek, cabbage, tea, parsley, oregano, spices and
nuts, and also in several non-cultivated plant species
(Nachbar and Oppenheim, 1980; Liener, 1986; Gupta and
Sandhu, 1998; Oliveira et al., 2000; Leontowicz et al.,
2001), the exposure of heterotroph organisms, including
human beings, to functionally active lectins is a common
event. Actually, the presence of nutritionally signiﬁcant
amounts of active lectins in fresh and processed foods and
the lack of public knowledge concerning the deleterious
effects of dietary lectins on the gut and health have led to a
number of outbreaks of food poisoning. For example, Noah
et al. (1980) reported seven incidents involving 43 persons
in which the poisonings were attributed to toxins present in
uncooked or partially cooked kidney beans (Phaseolus
vulgaris). In 1981, a television programme by BBC cited a
total of 330 outbreaks of kidney bean food poisonings
involving 880 people (Bender and Reaidi, 1982). In 1988, a
hospital launched a ‘healthy eating day’ in its staff canteen
at lunchtime. One dish contained red kidney beans and 31
portions were served. Between 3 and 7 pm, 11 customers
suffered from profuse vomiting and some diarrhoea. No
pathogens were isolated from the food, but the beans
contained abnormally high concentration of PHA (Gilbert,
1988). These examples all relate to kidney bean. However, it
is possible that there have been problems with other lectin-
containing foods that have not been reported.
3. Oral toxicity of plant lectins to higher animals
As already mentioned, the knowledge that some lectins
are toxic to animals dates back to 1888, when Stillmark
published his work on the deleterious effects of a
proteinaceous substance present in castor bean. Soon after
similar toxic substances were discovered in the seeds of
Croton triglium (crotin) and Abrus precatorius (abrin) and
in the bark of Robinia pseudoacacia (robinia) (Van Damme
et al., 1998). With the increasing interest on lectins
heightened particularly from the discovery of blood group
speciﬁcity (Renkonnen, 1948; Boyd and Reguera, 1949) and
from the realisation that PHA induced mitosis in mature,
non-dividing human lymphocytes (Nowell, 1960), many
other lectins were identiﬁed and isolated. Some of these
were found to be toxic or antinutritional for man and
animals. In general, nausea, bloating, vomiting and
diarrhoea characterize the oral acute toxicity of lectins on
humans exposed to them. In experimental animals fed on
diets containing plant lectins the evident symptoms are loss
of appetite, decreased body weight and eventually death
(Liener et al., 1986; Duranti and Gius, 1997; Lajolo and
Genovese, 2002). The mechanisms by which lectins mediate
toxicity and the characteristic which dictate whether a lectin
will be deleterious or not are not completely understood.
Nevertheless, from a nutritional viewpoint, it is important to
ﬁnd ways of identifying which lectin is and which is not
As an attempt to predict the oral toxicity of lectins using
small amounts of sample toward minimising costs and
reducing the experimental time, many lectins were tested for
toxicity by intradermal or intraperitoneal administration in
rats and mice (Liener, 1986, 1994; Reynoso-Camacho et al.,
2003). From these studies it emerged that whilst most
parentally toxic lectins were also orally toxic, a few
exhibited no oral toxicity. Contrarily some parenterally
non-toxic lectins were highly toxic when orally adminis-
tered. Therefore, intradermal or intraperitoneal tests
designed to evaluate oral toxicity are not a reliable predictor.
Furthermore, parenteral administration is not the common
route by which animals are exposed to dietary lectins. Data
currently available indicate that multiple exposure and long-
term studies may be also needed to address lectin toxicity
(Grant et al., 2000).
The ability of lectins to selectively bind to different types
of blood cells has also been proposed as a means to predict
oral toxicity of these proteins. It has been suggested that the
hemagglutinating ability could form a basis for in vitro
screening of potentially toxic lectins. Thus, lectins which
strongly agglutinate a wide range of different red blood cells
should generally have high oral toxicity for rats, whereas
those agglutinating only rabbit and/or enzyme-treated rat
erythrocytes should not (Grant et al., 1983, 1995). However a
lack of a signiﬁcant number of assays to ﬁrmly establish such
relationship together with exception to this rule found for
several lectins such as the Cratylia argentea lectin (CAA)
which strongly agglutinates a wide range of erythrocytes
being essentially non-toxic (Rios et al., 1996), mean that this
approach is not a reliable predictor. As with intradermal and
intraperitoneal toxicity studies, this procedure cannot be used
alone to predict which lectin will or will not have deleterious
effects when consumed orally. In fact, the unique reliable
way of predicting the oral toxicity of lectins is by feeding the
target animal on diets containing the puriﬁed lectin. More-
over, it is important to carry out these tests on several
different animal species and not just on rats and mice.
Accordingly, kidney beans induced pancreas growth in
chicks but not in pigs (Huisman et al., 1990a,b). Recently,
Douglas et al. (1999) detected that SBA (Glycine max;
soybean agglutinin) accounted for approximately 15% of the
growth depression from raw soybeans in chicks, whereas
Liener (1953) estimated that lectins accounted for approxi-
mately 50% of the growth-inhibiting effect of raw soybean
meal in rats. In addition, it has been considered that the
degree to which some lectins affect metabolism is, in part,
dependent on dietary history of the animal and the exact
composition of the diet (Grant, 1999). However, it is
impractical to test all lectins under all circumstances in
vivo. To establish a screening system, it is thus important to
develop a clear picture of the properties of speciﬁc lectins that
lead them to be toxic to man and animals.
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403 387
4. Resistance of lectins to proteolysis
Plant proteins are generally regarded as more resistant
to proteolysis than most proteins of animal origin (Fried-
man, 1996; Sgarbieri, 1996; El-Adawy, 2002). Indeed, the
apparent digestibility of proteins in vivo from leguminous
seeds and oilseeds in their raw state varies from 15.6% to
about 80% depending upon the origin (Grant et al., 1995;
Carbonaro et al., 2000; Preet and Punia, 2000; Cuadrado
et al., 2002). In contrast, animal proteins, such as egg
albumin or casein, are 85 – 94% digestible in vivo (Oliveira
et al., 1994; Vasconcelos et al., 2001). Many plant lectins
in particular have been found to be resistant to degradation
by proteases in vitro (Carbonaro et al., 1997) and in the gut
in vivo (Pusztai, 1991). This may in fact be a common
feature of this class of proteins. PHA (Pusztai et al., 1979;
Hara et al., 1984), ConA (Nakata and Kimura, 1985),
ConBr (Canavalia brasiliensis)(Oliveira et al., 1994),
CAA (Oliveira et al., unpublished data), PTA (Psopho-
carpus tetragonolobus; winged bean) (Higuchi et al.,
1983), LEA (Lycopersicon esculentum; tomato) (Kilpatrick
et al., 1985), GNA, SBA, WGA, PSA, SNA-I, SNA-II
(Sambucus nigra; elderberry), VFL (Vicia faba; broad
bean) and DGL (Dioclea grandiﬂora; mucuna) (Pusztai,
1991; Bardocz et al., 1995) were all showed to be resistant
to in vivo breakdown by proteolytic enzymes. The extent
of the in vivo lectin resistance to degradation by the gut
enzymes was variable but in some cases it reached very
high values. For instance, in one trial with rats fed on
known amounts of intragastrically administered pure
lectins, the feces were found to contain (by ‘rocket
immunoelectrophoresis’) over 90% of the ingested PHA,
ConA and GNA in a form still fully reactive towards rabbit
anti-lectin antibodies (Pusztai, 1991). Of a particular
interest is the ﬁnding that biologically intact WGA was
detected in ileostomy efﬂuent and fecal collections from
human subjects consuming a diet containing wheat germ
(Brady et al., 1978). These observations demonstrated that
PHA, ConA, GNA and WGA transverse the rat and human
small intestine, respectively, intact. Conceivably orally
ingested plant lectins remaining at least partially undi-
gested in the gut may bind to a wide variety of cell
membranes and glycoconjugates of the intestinal and
colonic mucosa leading to various deleterious effects on
the mucosa itself as well as on the intestinal bacterial ﬂora
and other inner organs (Ru
It is also noteworthy that far less of the lectins survive the
in vitro treatment with proteolytic enzymes (Rios et al.,
1996). This was the case for ConBr, CAA and DGL, all
glucose–mannose speciﬁc lectins, which were digested to a
far higher extent (52 – 84%) than in vivo. Thus, it is possible
that in the gut the lectins may even be protected from
proteolytic degradation during gut passage perhaps as a result
of binding to epithelial or lumenal gut components. The slight
protection from proteolytic degradation in vitro conveyed by
adding glucose, Ca
to the reaction mixture is
consistent with this possibility. Nevertheless, as a result of
high resistance to proteolytic degradation in vivo nutrition-
ally signiﬁcant amounts of certain dietary lectins will survive
in an intact and highly reactive form within the gut lumen.
Obviously this is crucial for them to exhibit the full
spectrum of their biological activities on animals (Fig. 1).
Fig. 1. Spectrum of biological activities of plant lectins on higher animals.
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403388
Thus the deleterious effects of lectins depend deﬁnitively on
the degree of lectin resistance to proteolytic degradation
5. Effects of lectins on the digestive tract
As most lectins are not degraded during their passage
through the digestive tract they are able to bind the epithelial
cells which express carbohydrate moieties recognised by
them. This event is undoubtedly the second one in
importance for determining the toxicity of orally fed lectins.
Indeed, lectins which are not bound by the mucosa usually
induce little or no harmful antinutritive effect for the
consumers (Pusztai and Bardocz, 1996). Once bound to
the digestive tract, the lectin can cause dramatic changes in
the cellular morphology and metabolism of the stomach and/
or small intestine and activate a cascade of signals which
alters the intermediary metabolism. Thus, lectins may induce
changes in some, or all, of the digestive, absorptive,
protective or secretory functions of the whole digestive
system and affect cellular proliferation and turnover. In 1960,
´suggested that the toxic effects of ingested lectins were
due to their ability to combine with speciﬁc receptor sites of
the cells lining the small intestine and to cause a non-speciﬁc
interference with absorption and nutrient utilisation (Jaffe
1960). Many observations either in vivo or in vitro support
´’s hypothesis (Oliveira et al., 1988; Hajos et al., 1995).
PHA was also able to attach to gastric mucosal and parietal
cells inhibiting the gastric acid secretion in conscious rats
´s et al., 2000, 2001). Additionally, PHA-treated pigs
showed an increase in stomach weights and mucosa thickness
(Radberg et al., 2001). In fact, if appropriate carbohydrate
moieties are expressed on the surface of any structure or
organ, lectins will be able to bind to them (Pusztai, 1991;
Jordinson et al., 1997; Otte et al., 2001; Bryk and Gheri,
2002). Moreover, in rats some lectins appeared to progress-
ively mediate changes in the glycosylation of the gut leading
to an increase in the binding sites to which they could attach
(Pusztai et al., 1995). As the glycosylation state of the gut
among higher animals shows many similarities it is plausible
to suppose that the adverse effects of dietary lectins observed
on experimental animals will be comparable in human
beings. Obviously the severity of these adverse effects will
depend on the gut region to which the lectin will bind
(Baintner et al., 2000).
Many lectins either directly or indirectly cause profound
morphological and physiological modiﬁcations in the small
intestine. Such alterations characteristically lead to
increased shedding of brush border membranes, accelerated
cell-loss and shortened, sparse and irregular enterocyte
microvilli (Pusztai, 1991; Bardocz et al., 1995; Herzig et al.,
1997). In fact, binding of lectins to the gut epithelium is
frequently accompanied by disruption of the brush borders
and disorganisation of the main absorptive cells, which
cause reduction in the absorptive surface area and absorp-
tion of nutrients. One result of this is cellular hyperplasia
and increased endogenous secretion leading to large
increases in the small intestinal weight of rats fed lectins
(Otte et al., 2001; Sasaki et al., 2002). Actually some lectins
have been shown to trigger notable trophic effects on the
intestine. PHA and PNA consistently reversed the fall in
gastrointestinal and pancreatic growth associated with total
parenteral nutrition by stimulating the release of speciﬁc
hormones, such as gastrin, cholecystokinin (CCK) and
enteroglucagon (Jordinson et al., 1999). Parenteral admin-
istration of ConA signiﬁcantly elevated epithelial cell
proliferation in the rat intestine (Fitzgerald et al., 2001).
Regardless of the precise nature of the initial response by the
small intestinal cells to the growth signal, it is clear that
there is an obligatory accumulation of polyamines, such as
putrescine, spermidine and spermine, in small crypts
(Pusztai, 1991; Bardocz et al., 1996). This is followed by
secondary responses, which include increased DNA, RNA,
protein and carbohydrate tissue contents (Pusztai et al.,
1988; Bardocz et al., 1995). Increased rat small intestinal
weight has also been related to SBA, ConA, ConBr, WGA
and PNA (peanut agglutinin) (Pusztai, 1991; Grant, 1991,
1999). A dramatic dose-dependent hyperplastic growth of
the small intestine was also observed by oral administration
of ML-1 (Viscum album; mistletoe lectin), probably due to
the avid binding and endocytosis of this lectin by gut
epithelial cells (Pusztai et al., 1998). In contrast, no weight
effect was found for the small intestine in the PHA-treated
pigs. However, morphometric analyses of the small intestine
of these animals showed a decrease in villus heights, an
increase in crypt depths and crypt cell mitotic indices, fewer
vacuolated enterocytes per villus and reduced vacuole size.
Additionally, a decrease in the absorption of different-sized
marker molecules after gavage feeding and a decrease in
intestinal marker permeability were observed (Radberg
et al., 2001). PHA also induces growth of the large intestine
(Bardocz et al., 1995). Nevertheless, in this digestive tract
section the changes were much less marked than those
observed in the small intestine (Grant, 1999).
In addition to the disruptive effects on cell membrane,
lectins have been shown to inhibit various intestinal and
brush border enzymes. A non-competitive inhibition of
enterokinase from rat duodenal brush borders was observed
in vitro in the presence of ConA, PHA or SBA, PHA being
the most potent inhibitor (Rouanet et al., 1983). PHA also
interacted and inhibited brush border dipeptidase in vitro
(Erickson et al., 1985). Sucrose, maltase, alkaline phospha-
tase, leucine aminopeptidase and g-glutamyltransferase, all
suffered a signiﬁcant decrease in activities by inclusion of
PTA in a basal diet offered to rats (Higuchi et al., 1984).
RCA (R. communis), PHA and UEA interacted with various
human small intestine brush-border hydrolases such as
sucrase, isomaltase, maltase glucoamylase, lactase, neutral
and acid aminopeptidases and dipeptidyl peptidase IV
(Triadou and Audran, 1983). PHA decreased the hydrolysis
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403 389
of casein, bovine serum albumin and heat-treated bean
extract by pepsin and pancreatin (Thompson et al., 1986).
The insecticidal GNA given to pathogen-free rats increased
the activities of the brush border enzymes alkaline
phosphatase and aminopeptidase whereas sucrase– isomal-
tase activity was nearly halved (Pusztai et al., 1996). ASA,
the lectin from edible garlic (Allium sativum), induced
increased activities of disaccharidases and acid phosphatase
in the rat jejunum whereas the activities of alkaline
phosphatase, lactate dehydrogenase and adenosine tripho-
sphatase were lower (Gupta and Sandhu, 1998). Thus, the
well established lectin-induced disruption of intestinal
microvilli combined with the in vivo inhibitory effects on
gut enzymes suggest that the lectins interfere, either directly
or indirectly, not only with the utilisation of dietary protein
and carbohydrate but also with the initial and ﬁnal stages of
protein/carbohydrate digestion and transport.
An additional secondary toxic effect of undigested
lectin, particularly PHA, in the small intestine which may
further reduce the efﬁciency of digestion and absorption
of food is a dramatic overgrowth of coliform bacteria
(Wilson et al., 1980; Pusztai et al., 1993a; Bardocz et al.,
1996). The mechanism by which lectins promote
proliferation of coliforms, mainly Escherichia coli,is
not fully understood. However, it has been established
that in relation to PHA, the bacterial proliferation arises
primarily as a result of its effects on epithelial cell
metabolism (Pusztai, 1991; Pusztai et al., 1995). Indeed
PHA-mediated mucus secretion, epithelial cell loss,
serum protein leakage and reduced digestion of dietary
protein possibly further aid bacterial proliferation by
providing a good source of nutrients (Grant, 1999). In
consequence, the increase in bacterial numbers in the
small intestine may lead to overproduction of bacterial
toxins which also contributes to the worsening of animal
Although almost all the theory about the general
deleterious effects of dietary lectins on animals was built
from various comprehensive studies carried out with PHA,
other lectins showed some similar effects. We showed that
ConBr, a lectin from Canavalia brasiliensis, which shares
90% amino acid sequence similarity with ConA (Grangeiro
et al., 1997), inhibited rat growth probably through
interference in the metabolism as elevated losses of
nitrogen and dry matter in the feces and lower retention
of ingested nitrogen were observed (Oliveira et al., 1994).
Recently, we observed that another ConA related lectin,
CAA (Cratylia argentea agglutinin), interacted with the
epithelium of duodenum, jejunum and ileum of rats fed on
diets containing the C. argentea seed meal or CAA at 2%
protein level. CAA-binding to the cells lining the gut
lumen (Fig. 2) may have signiﬁcantly impaired nutrient
absorption which led to a reduced body weight gain in such
animals, higher fecal and nitrogen outputs and lower
6. Systemic effects of dietary lectins
High rates of internalisation of dietary lectins by
enterocytes after binding to the small intestine cells appear
to be a common event (Pusztai, 1991; Bardocz et al., 1995).
Lectins, which bind to epithelial cells, may be taken up into
cells by endocytosis, be released by exocytosis into the
intracellular space from where they are subsequently
transported throughout the body. As a result, reactive
forms of the lectins are distributed in the circulation and
internal tissues and may lead to deleterious systemic effects.
For instance, the N-acetylglucosamine-speciﬁc agglutinins,
WGA, UDA and DSA (Datura stramonium; thorn apple),
when offered to rats at the level of 7 g/kg diet, bound to and
were endocytosed by the epithelial cells of the small
intestine (Pusztai et al., 1993b). An appreciable portion of
the endocytosed WGA, the most damaging amongst the
three lectins tested, was transported across the gut wall into
the systemic circulation where it was deposited in the walls
of the blood and lymphatic vessels (Pusztai et al., 1993b).
PHA was found to induce a powerful, selective humoral
response of the IgG-type when raw beans were fed to rats
Fig. 2. Light micrograph (600 £) of a duodenum villus of a rat fed
for 10 days on a diet containing 2% Cratylia argentea seed lectin.
Incubation of a duodenum transverse section with rabbit anti-lectin
immunoglobulins and alkaline phosphatase-conjugated goat anti-
rabbit IgG produced a dark staining on the villus surface
representing the immunolabelling lectin bound to a mature
enterocyte. No enterocyte staining was observed in control rats
fed on an egg white based diet.
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403390
(Grant et al., 1985), growing steers (Williams et al., 1984)
and pigs (Begbie and King, 1985), indicating its absorption
through the gut wall. However, development of circulating
antibodies to the lectin was unable to prevent either
bacterial proliferation or the uptake of the dietary lectin
into the systemic circulation (Pusztai, 1989). For instance,
the presence of antibodies from human blood against the
banana lectin (BanLec-1) was detected in a screening for
reactivity to foodstuff components (Koshte et al., 1990,
1992). Circulating antibodies to three structurally related
legume lectins, ECorL (Erythrina corallodendron), PNA
and SBA, and to WGA were puriﬁed by lectin-afﬁnity
chromatography from human sera indicating that antibodies
to dietary lectins commonly present in human diets exist in
the sera of healthy humans (Tchernychev and Wilchek,
1996). The authors argued that the signiﬁcant amounts of
circulating antibodies which reacted with EcorL, as it is not
a dietary protein, is because legume lectins share consider-
able structural similarities (Van Damme et al., 1998).
Recently, the mucosal immunogenicity of a number of plant
lectins, with different sugar speciﬁcities, was investigated in
mice (Lavelle et al., 2000). Accordingly both oral and
intranasal delivery of ﬁve plant lectins, LEA, ML-1, PHA,
WGA and UEA-1, stimulated the production of speciﬁc
serum IgG and IgA antibodies after three intranasal or oral
The ability of most plant lectins to transverse the gut
barrier is not limited to antibody production but can also
trigger histamine release from basophils (Haas et al., 1999).
Accordingly 16 common lectins, particularly ConA, PHA,
PSA, SNA and LCA (Lens culinaris; lentil) were able to
induce human basophils to secrete interleukin-4 (IL-4) and
IL-13, the key promoters of Th2 responses and IgE
synthesis. Since lectins can enter the circulation after oral
uptake, they might play a role in inducing the so-called early
IL-4 required to switch the immune response towards a Th2
response and type I allergy.
In a recent review, Cordain et al. (2000) stated that the
interaction of dietary lectins with enterocytes and lympho-
cytes might facilitate the translocation of both dietary and
gut-derived pathogenic antigens to peripheral tissues
causing a persistent peripheral antigenic stimulation in
genetically susceptible individuals. This might ultimately
result in the expression of overt rheumatoid arthritis (RA).
A striking anatomical change evident in rats fed on
lectins is the severe atrophy of the thymus. This occurs to
disappeared after feeding PHA for 10 days (Oliveira et al.,
1988, 1994). Although the precise signiﬁcance of this
involution is not clear, it is quite likely that it may affect
cell-mediated immune responses having serious conse-
quences for the animal. Thus, the proliferation of normally
innocuous intestinal bacteria and even the absorption of an
antigenic form of lectin which has been shown to gain entry
to the systemic circulation are possibly related to
the incapacity of these animals to develop an adequate
humoral and cell-mediated immune response.
Usually animals fed on legume diets develop pancreas
hypertrophy. Formerly this phenomenon had been exclu-
sively associated to dietary protease inhibitors. Studies by
Oliveira et al. (1988) and Pusztai et al. (1988) unequivocally
showed that the puriﬁed PHA included into diets offered to
rats promoted hypertrophy of the pancreas in a dose
response fashion. This was in fact the ﬁrst time that
pancreatic hypertrophy was shown to be due to diets which
contained puriﬁed lectins free from trypsin inhibitors. Since
then, this effect has consistently been observed in rats fed on
different diets containing puriﬁed lectins from other
legumes (Oliveira et al., 1994; Vasconcelos et al., 2001).
Recently Kelsall et al. (2002) demonstrated in long-term
feeding trials that even low doses (40 mg/rat/day) of PNA
given to rats could signiﬁcantly inﬂuence pancreatic growth.
They suggested that this trophic action might have potential
adverse implications for the development of pancreatic
cancer in humans. Accumulation of polyamines has been
shown to precede organ hypertrophy (Pusztai et al., 1988;
Bardocz et al., 1996). Further PHA, SBA, PNA and WGA-
induced pancreatic growth of rats, in vivo, are related to
increasing CCK plasma levels with corresponding increase
in pancreatic protein output suggesting that the ingestion of
lectins might have major CCK-mediated effects on
gastrointestinal function and pancreas growth (Herzig
et al., 1997; Jordinson et al., 1997). CCK is a peptide
hormone released from the I-cells of the upper small
intestine which is a potent stimulator of various physiologi-
cal functions such as pancreas enzyme secretion, reduction
of food intake, inhibition of gastric emptying and stimu-
lation of gall bladder contraction (Sayegh and Ritter, 2003).
Grant et al. (1999) suggested that secretion of pancreatic
digestive enzymes induced in rats by ﬁrst-time oral exposure
to PHA (E
isolectin) was mediated only in part by CCK.
They suggested that additional mechanisms or hormones,
such as secretin, might play a role in modulating later
exocrine pancreas responses to PHA. PHA was also able to
stimulate pancreatic amylase secretion in rats which was
blocked by devazepide, a CCK-A receptor antagonist
´s et al., 2000). Radberg et al. (2001) observed that
the size of the pancreatic acini was greater in the PHA-
treated pigs, but no increases in enzyme content or
pancreatic weight could be determined. However, the
blood plasma levels of CCK were higher in the PHA-
treated than in the control pigs.
Disturbances of the hormonal homeostasis of animals
were also observed upon feeding lectins. PHA reduced the
circulating levels of insulin initially by interfering with its
secretion from the pancreas but later insulin synthesis was
also impaired. Surprisingly, normal blood glucose concen-
trations were maintained in rats fed with PHA despite the
low circulating insulin levels (Pusztai, 1991; Bardocz et al.,
1996). The exact mechanism by which lectins cause changes
in insulin production remains unclear. However, it is
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403 391
possible that through its binding to neuroendocrine cells in
the gut or to other non-pancreatic endocrine organs, PHA
may trigger the release of hormones which impair insulin
synthesis/secretion. Alternatively, it is likely that the
insulin-mimicking properties of lectins in vivo may interfere
with the feedback regulation of pancreatic insulin pro-
duction (Bardocz et al., 1996).
Liver enlargement was shown to be another systemic
effect of dietary lectins (Oliveira et al., 1988; Pusztai, 1991).
The increase in liver weight may be due to a response of this
organ to the disturbance of the general metabolism that
occurs when animals are fed with lectins. In fact some
lectins induce body fat catabolism and glycogen loss,
leading to depletion of the body reserves (Grant et al., 1987,
1995). Dietary PHA, for instance, induces an increase in
body lipid utilization. A direct correlation between dietary
PHA and increased amounts of urinary 3-hydroxybutyrate
output of rats was observed, providing a strong evidence for
the occurrence of a PHA-dependent increased lipolysis
(Oliveira et al., 1988). The lipid depletion occurred
primarily from the adipose tissues whereas little change
was observed in liver lipid levels. In contrast, the glycogen
content of the liver was halved whereas the glycogen
concentration in skeletal muscle was not signiﬁcantly
affected during the same period (Oliveira et al., 1988;
Pusztai, 1989). According to Pusztai et al. (1998) ML-1
reduced body fat reserves probably through depression of
circulating insulin levels. Dietary PHA also alters the rate of
muscle protein synthesis without signiﬁcantly affecting the
rate of protein degradation, resulting in loss of muscle
weight (Palmer et al., 1987). It is possible that circulating
lectin may have interacted directly with muscle cells leading
to impairment of protein synthesis (Pusztai et al., 1989).
Alternatively, this effect may have been indirect and
hormonally mediated (Pusztai, 1991). Moreover, increased
concentration of urinary N (mainly urea-N) was observed in
PHA-fed rats suggesting disturbances in the protein
metabolism (Oliveira et al., 1988). Increased activities of
liver glutamic pyruvic transaminase (LGPT) and glutamic
oxaloacetic transaminase (LGOT), indicative of increased
catabolism of amino acids in the liver, were also observed
when increasing amounts of dietary PLA (Phaseolus
lunatus; lima bean) were offered to rats (Aletor and Fetuga,
1985). In summary, dietary lectins seem to interfere with the
overall metabolism of body lipid, protein and carbohydrate
(Pusztai, 1991; Grant, 1999). Such effects may have a
bearing upon hepatomegaly. Although the signiﬁcance of
the morphological and metabolic changes in the liver of
lectin-fed animals remains to be elucidated, such adverse
effects upon this key organ certainly contribute to the overall
toxicity of dietary lectin.
Lung hypertrophy was also detected in rats fed with
diets containing ML-1 (Pusztai et al., 1998). Peanut
lectin which displays afﬁnity for glycoproteins found
speciﬁcally on arterial smooth muscle cells stimulated the
growth of smooth muscle and pulmonary arterial cells,
suggesting that biologically active PNA present in peanut
oil could possibly contribute signiﬁcantly to its athero-
genic properties (Kritchevsky et al., 1998).
Recently our group puriﬁed a toxic and hemagglutinat-
R. et Schult., Convolvulaceae) leaves which agglutinates
rabbit, horse and ovine red cells but not cow, sheep, goat,
dog and human erythrocytes. This activity was not abolished
by simple sugars but fetuin, avidin and N-acetyl-D-
neuraminic acid were inhibitory (Santos, 2001). IAAL
injected intraperitoneally into mice and rats induced
dyspnoea, tonic–clonic convulsions and ﬂaccid paralysis
prior to death. IAAL was also toxic to orally fed mice. When
IAAL was daily intubated into female mice, for 15 days, it
induced stunted growth, diarrhoea, severe respiratory
distress and muscle tremors. The liver of the female mice
receiving IAAL showed megalocytose and hepatocytes with
vacuolar degeneration and piknotic nuclei. In the kidneys,
tubular liquefactive necrosis, atrophy and destruction of
glomeruli and congestion of blood vessels occurred (data
not shown). Surprisingly, the litter was also affected with
some of these above symptoms (Fig. 3), although in a lesser
Despite the adverse effects of dietary lectins, in recent
years, considerable work has been done on the possible uses
of them, at non-toxic oral doses, to obtain therapeutically
beneﬁcial effects, such as promotion of gut regrowth after
total parenteral nutrition or exposure to elemental diets
(Jordinson et al., 1999; Sasaki et al., 2002), use as drug
delivery agents or oral vaccine adjuvants (Lavelle, 2001;
Lavelle et al., 2001) or use in anti-cancer therapies (Pryme
et al., 1998, 1999).
Fig. 3. Light micrograph (100 £) of kidney section from a suckling
mouse pup whose mother was intubated for 15 days with
Ipomea asarifolia agglutinin (IAAL, 6–8 mg/day/mouse) showing
blood vessel congestion (BVC), glomerulus atrophy (GA) and
tubular necrosis (TN).
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403392
7. Insecticidal properties of plant lectins
The insecticidal activity (Table 1) of plant lectins against
a large array of insect species belonging to the Coleoptera,
Homoptera, Diptera and Lepidoptera order has been well
documented (Gatehouse et al., 1995; Schuler et al., 1998;
Carlini and Grossi-de-Sa
´, 2002). This feature represents a
potential of using plant lectins as naturally occurring
insecticide agents against the pests which restrain increased
crop production. Generally the in vitro bioassay undertaken
to judge this biological characteristic consists of inclusion of
the studied lectin into artiﬁcial diets offered to the target
insect during a given period of time. In general, the lectin
levels incorporated into artiﬁcial diets to test oral toxicity
have varied from 1 to 50 mg/g diet or from 5 to 1500 mg/ml
diet to deliver these proteins to chewing and sucking insects,
respectively. Then, the parameters which indicate the
harmful effects of lectins on insects include larval weight,
size, color, mortality, feeding inhibition, antimetabolic
effects, honeydew excretion levels, pupation, delays in
total developmental time, adult emergence and/or fecundity
on the ﬁrst and/or second generation of the insects which
have been reared on lectin-containing artiﬁcial diets.
Although the precise mode of insecticidal action of plant
lectins is not fully understood it appears that resistance to
proteolytic degradation by the insect digestive enzymes and
binding to insect gut structures are two basic prerequisites
for lectins to exert their deleterious effects on insects. As in
higher animal systems (Pusztai, 1991), the harmful effects of
lectins on insects are attributed mainly to binding of them to
the surface of the intestinal epithelial cells which lead to
interference with the digestive, protective, or secretory
functions of the intestine. Nevertheless, it is quite obvious
that for binding to the intestine structures, cells and/or to any
digestive enzyme or either to other insect component, the
orally fed lectins have ﬁrstly to be refractory to the action of
proteolytic enzymes and, in addition, to encounter satisfac-
tory environmental conditions of pH and temperature to
exert their effects. Indeed, structure/function analysis by
site-directed mutagenesis indicated that the insecticidal
and binding activities of the GlcNAc-speciﬁc lectin GSII
(Griffonia simplicifolia) and its mutant forms were corre-
lated with the resistance to proteolytic degradation by the
midgut extracts and binding to the digestive tract of third or
fourth instar larvae of Callosobruchus maculatus (Coleop-
tera: Bruchidae), the cowpea weevil. This insect when
reared on a GSII-containing artiﬁcial diet had a within-seed
prolonged development time and inhibited growth (Zhu-
Salzman et al., 1998). These effects may have resulted from
the binding of this lectin to the chitin of the peritrophic
membrane, a structure existing in the gut of most
phytophagous insects which protects the gut epithelial
cells from abrasive food particles (Peumans and Van
Damme, 1994). It is likely that other GlcNAc-speciﬁc
lectins (Table 1) share similar mode of action on insects.
The two chitin-binding lectins, TEL and KpLec, from
Talisia esculenta and Koelreuteria paniculata seeds,
respectively, negatively affected the larval development of
C. maculatus and Anagasta kuehniella (Lepidoptera:
Pyralidae; Mediterranean ﬂour moth) through binding to
glycan receptors on the surface of cells lining the insect gut
(Macedo et al., 2002, 2003). Regression analysis showed
that for every 0.1% increase in TEL dose given via artiﬁcial
seeds, there were a 3.9% ðR2¼0:98Þand 4.1% ðR2¼0:99Þ
increase in mortality of C. maculatus and Zabrotes
subfasciatus (Coleoptera: Bruchidae), respectively (Macedo
et al., 2002) whereas for every 0.1% increase in KpLec dose,
there were a 5.9% ðR2¼0:98Þand 5.3% ðR2¼0:96Þ
increase in mortality of C. maculatus and Anagasta
kuehniella, respectively (Macedo et al., 2002). Immuno-
logical studies carried out to elucidate the mechanism of
action of the mannose-speciﬁc lectin GNA on the rice brown
planthoppers (Nilaparvata lugens; Homoptera: Delphaci-
dae) showed that no signiﬁcant proteolytic degradation
occurred either in the gut or honeydew of insects fed on
lectin-containing diet (Powell et al., 1998). The fully active
GNA was able to bind to the luminal surface of the midgut
epithelial cells within the planthopper, probably recognising
cell surface carbohydrate moieties of glycoproteins and/or
other glycoconjugates in the gut. For instance, the mannose-
containing glycopolypeptide ferritin acts as the most
abundant binding protein for GNA in the midgut of rice
brown planthoppers (Du et al., 2000). Moreover the
immunolabelling GNA assay revealed its presence in the
fat bodies, the ovarioles, and throughout the haemolymph
suggesting that GNA was able to cross the midgut epithelial
barrier and pass into the insect’s circulatory system
resulting in a systemic toxic effect (Powell et al., 1998).
Resistance to proteolytic degradation and binding of
ASAL (mannose-binding leaf garlic lectin) to gut receptors
in the luminal epithelium of two important homopteran
insect pests, the mustard aphid (Lypaphis erysimi; Aphidi-
dae: Homoptera) and the red cotton bug (Dysdercus
cingulatus; Hemiptera: Pyrrhocoridae) also correlated with
its insecticidal activities (Bandyopadhyay et al., 2001).
ASAL bound to the carbohydrate residue of the 55 and
45 kDa brush border membrane vesicle receptor proteins in
the case of aphid and bug, respectively, possibly decreasing
the insect membrane permeability. Zhu-Salzman and
Salzman (2001) studying the digestion of recombinant
GSII and its mutant protein variants with two puriﬁed
cathepsin L-like gut proteases of C. maculatus larvae
suggested that carbohydrate binding to the insect gut and
proteolytic resistance are independent properties of rGSII.
However they concluded that both properties facilitate GSII
efﬁcacy as a plant defensive molecule. GNA and ConA
when included in artiﬁcial diets offered to the tomato moth
(Lacanobia oleracea; Lepidoptera: Noctuidae) larvae accu-
mulated in the gut, Malpighian tubules and haemolymph
indicating that both lectins were internalised and distributed
systemically after binding to glycoproteins present along the
insect digestive tract (Fitches et al., 2001a).
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403 393
Plant lectins with oral toxicity to insect
Lectin (plant source) Insect Host Reference
ASA (Allium sativum)Laodelpha striatellus (rice
small brown planthopper);
Nilaparvata lugens (rice
Rice Powell et al., 1995
Myzus persicae (peach-
Peach, potato Sauvion et al., 1996
Dysdercus cingulatus (red
cotton bug); D. koenigii (red
Cotton, okra, maize, pearl Roy et al., 2002
ASA I, II D. cingulatus;D. koenigii Cotton, okra, maize, millet Roy et al., 2002
ASAL (Allium sativum—leaf) D. cingulatus;Lipaphis erysimi
Cotton, okra, maize, pearl Bandyopadhyay et al.,
CEA (Colocasia esculenta)D. cingulatus;D. Koenigii Cotton, okra, maize, pearl Roy et al., 2002
DEA (Differenbachia sequina)D. Cingulatus;D. Koenigii Cotton, okra, maize, pearl Roy et al., 2002
GNA (Galanthus nivalis)Callosobruchus maculatus
Cowpea Gatehouse et al., 1991
Acyrthosiphon pisum (pea aphid) Pea Rahbe
´et al., 1995
Sugarcane Allsopp and McGhie,
(glasshouse potato aphid)
Potato Down et al., 1996
M. persiacae Peach, potato Sauvion et al., 1996
Lacanobia oleracea (tomato moth) Tomato Fitches and Gatehouse,
1998; Fitches et al.,
Maruca vitrata (legume pod-bore) Cowpea Machuka et al., 1999
Taro Powell, 2001
L. striatellus Rice Loc et al., 2002
N. lugens Rice Powell et al., 1995,
1998; Loc et al., 2002
KPA (Koelreuteria paniculata)Anagasta kuehniella (Mediterranean
ﬂour moth); C. maculatus
Beans, grains, fruits, nuts Macedo et al., 2003
LOA (Listera ovata)M. vitrata Cowpea Machuka et al., 1999
NPA (Narcissus pseudonarcissus)N. lugens Rice Powell et al., 1995
M. persiacae Peach, potato Sauvion et al., 1996
ConA (Canavalia ensiformis)A. pisum Pea Rahbe
A. pisum Pea Rahbe
´et al., 1995
Aphis gossypii (cotton and
Cotton, mellon Rahbe
´et al., 1995
Aulacorthum solani (glasshouse
and potato aphid)
´et al., 1995
´et al., 1995
Apple, bean, broccoli, papaya Rahbe
´et al., 1995
M. persiacae Peach, potato Rahbe
´et al., 1995;
Sauvion et al., 1996;
Gatehouse et al., 1999
L. oleracea Tomato Fitches and Gatehouse,
1998; Gatehouse et al.,
1999; Fitches et al.,
(continued on next page)
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403394
A toxic dose of GNA was also able to induce
morphological changes in the midgut region of planthoppers
with disruption of the microvilli brush border region (Powell
et al., 1998). Habibi et al. (2000) showed that the gut
epithelial cells of Lygus hesperus (Hemiptera: Miridae), the
Western tarnished plant bug, were severely disrupted by
PHA. Strong binding of PHA to the brush border microvilli
of the midgut at the ﬁrst and third, but not the second
ventriculus, and lectin internalisation were detected.
Moreover the ﬁrst ventriculus showed severe disruption,
disorganisation and swelling toward the proximal and distal
gut lumen regions which were completely closed. Complete
closure of the gut lumen also occurred in the hindgut region
as a consequence of severe disruption and swelling of
hindgut epithelial cells. However, only slight disruption
with enlargement of nuclei occurred in the foregut epithelial
cells clearly indicating that Lygus hesperus contains PHA
receptors in three speciﬁc regions of its digestive tract.
Table 1 (continued)
Lectin (plant source) Insect Host Reference
T. proserpina Taro Powell, 2001
LCA (Lens culinaris)A. pisum Pea Rahbe
´et al., 1995
PSA (Pisum sativum)A. pisum Pea Rahbe
´et al., 1995
Hypera postica (clover leaf weevil) Alfafa, lucerne Elden, 2000
ACA (Amaranthus caudatus)A. pisum Pea Rahbe
´et al., 1995
BSA (Bandeiraea simplicifolia)Diabrotica undecimpunctata (Southern
corn rootworm); Ostrinia nubilaris
(European corn borer)
Corn Czapla and Lang, 1990
BSAII A. pisum Pea Rahbe
´et al., 1995
GSII (Griffonia simplicifolia)C. maculatus Cowpea Zhu et al., 1996;
Zhu-Salzman et al.,
and Salzman, 2001
PAA (Phytolacca americana)D. undecimpunctata;O. nubilaris Corn Czapla and Lang, 1990
TEL (Talisia esculenta)C. maculatus; Zabrotes subfasciatus
(Mexican dry bean weevil)
Beans Macedo et al., 2002
WGA (Triticum aestivum)D. undecimpunctata;O. nubilaris Corn Czapla and Lang, 1990
Antitrogus sanguineus (sugarcane whitegrub) Sugarcane Allsopp and McGhie, 1996
H. postica Alfafa Elden, 2000
L. erysimi Mustard Kanrar et al., 2002
AHA (Artocarpus hirsuta)Tribolium castaneum (red ﬂour beetle) Large number of grains Gurjar et al., 2000
AIA (Artocarpus integrifolia)D. undecimpunctata;O. nubilaris Corn Czapla and Lang, 1990
GHA (Glechoma hederacea - leaf) Leptinotorsa decemlineata (colorado
Potato Wang et al., 2003
(Ricinus communis)D. undecimpunctata;O. nubilaris Corn Czapla and Lang, 1990
YBA (Sphenostylis stenocarpa)Clavigralla tomentosicollis (coreid bug) Vigna spp. Okeola and Machuka,
C. maculatus;M. vitrata Cowpea Machuka et al., 2000
ACA (Amaranthus caudatus)A. pisum Pea Rahbe
´et al., 1995
BFA (Brassica fructiculosa)Brevicoryne brassicae (cabbage aphid) Broccoli, Brussels sprouts,
cauliﬂower, head cabbage
BPA (Bauhinia purpurea)D. undecimpunctata;O. nubilaris Corn Czapla and Lang, 1990
CFA (Codium fragile)D. undecimpunctata;O. nubilaris Corn Czapla and Lang, 1990
EHA (Eranthis hyemalis)D. undecimpunctata Corn Kumar et al., 1993
MPA (Maclura pomifera)D. undecimpunctata;O. nubilaris Corn Czapla and Lang, 1990
PTA (Psophocarpus tetragonolobus)C. maculatus Cowpea Gatehouse et al., 1991
N. lugens Rice Powell, 2001
SNA-II (Sambucus nigra)A. pisum Pea Rahbe
´et al., 1995
VVA D. undecimpunctata;O. nubilaris Corn Czapla and Lang, 1990
PHA (Phaseolus vulgaris)L. hesperus (Western tarnished plant bug) Cotton, alfafa, legumes Habibi et al., 2000
Sugar speciﬁcity is represented by the best monosaccharide inhibitor.
Complex carbohydrate structure bearing terminal galactose residues (Goldstein and Poretz, 1986).
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403 395
Another additional antinutritional complication for the
insects fed on lectin-containing artiﬁcial diets of plants,
which also occurs in lectin-fed higher animals, is the
possibility that lectins may destabilise insect metabolism
by interfering with gut enzymatic function either
indirectly or by binding to glycosylated digestive enzymes
in the gut (Van Damme et al., 1998). Orally-fed GNA and
ConA, for example, affected the activities of soluble and
brush border membrane enzymes in the midgut of
Lacanobia oleracea larvae. Furthermore signiﬁcantly
elevated total aminopeptidase activity, both in terms of
total activity per larval gut and activity per mg gut
protein, was observed. Similarly, both GNA and ConA
treatments resulted in elevated levels of trypsin activity
per gut. GNA, but not ConA, induced a signiﬁcant
increase in a-glucosidase activity per gut. Thus lectins
upon binding to the gut may indirectly affect the enzyme
regulatory mechanisms as a consequence of perturbation
of the peritrophic matrix and/or brush border membrane
environment (Fitches and Gatehouse, 1998).
The major insecticide resistance mechanism in the
brown planthopper Nilaparvata lugens involves overpro-
duction of esterase isoenzymes. All the esterases puriﬁed
from an insecticide resistant strain of this insect were shown
to be glycosylated. As GNA, MAA (Maackia amurensis
agglutinin) and DAS (Diffenbachia sequina agglutinin) bind
to this family of esterases at the terminally linked mannose
(Small and Hemingway, 2000). It is possible that in trans-
genic plants expressing mannose-binding lectins, if they
were not fully effective in protecting the plant against the
brown planthopper (or other insecticide resistant pest), they
could interact with and inhibit the enzymes thereby
Plant species transformed with lectin genes to confer resistance against insects
Transformed plant Lectin
Target pest Reference
Maize WGA Ostrinia nubilaris;
Maddock et al., 1991
Mustard (B. juncea) WGA Lipaphis erysimi Kanrar et al., 2002
Arabidopsis thaliana PHA-E, L
Lacanobia oleracea Fitches et al., 2001b
Potato GNA Aulacorthum solani Down et al., 1996
Potato GNA Myzus persicae Gatehouse et al., 1996;
Couty et al., 2001b
Potato GNA L. oleracea Fitches et al., 1997;
Gatehouse et al., 1997
Potato GNA L. oleracea Bell et al., 1999, 2001;
Down et al., 2001
Potato GNA Aphidius ervi (parasitoid
of M. persicae)
Couty et al., 2001b
Potato ConA L. oleracea;M. persicae Gatehouse et al., 1999
Rice GNA Nilaparvata lugens Rao et al., 1998; Foissac et al.,
2000; Tinjuangjun et al., 2000;
Maqbool et al., 2001; Tang et al.,
2001; Loc et al., 2002
Rice GNA Nephotettix virescens (green
Foissac et al., 2000
Rice GNA Cnaphalocrocis medinalis (rice
leaffolder); Scirpophaga incertulas
Maqbool et al., 2001
Rice GNA Laodelphax striatellus (rice small
Sun et al., 2002; Wu et al., 2002
Sugarcane GNA Eoreuma loftini (Mexican rice borer);
Diatraea saccharalis (sugarcane borer)
Setamou et al., 2002
Sugarcane GNA Parallorhogas pyralophagus (parasitoid
of E. loftini)
Tomov and Bernal, 2003
Tobacco PSA Heliothis virescens (tobacco budworm) Boulter et al., 1990
Tobacco GNA M. persicae Hilder et al., 1995
Tobacco GNA Helicoverpa zea (cotton bollworm) Wang and Guo, 1999
Wheat GNA Sitobion avenae (grain aphid) Stoger et al., 1999
For lectin abbreviations see Table 1.
Transgenic Arabidopsis plants expressing the Phaseolus vulgaris erythro- and leucoagglutinating isolectins (PHA-E and PHA-L) either at
0.4–0.6% of total soluble proteins were not toxic to L. oleracea.
First demonstration of insect enhanced resistance of transgenic plants expressing a foreign lectin.
I.M. Vasconcelos, J.T.A. Oliveira / Toxicon 44 (2004) 385–403396
rendering the insect more susceptible to the action of
insecticide. This could reduce the amounts of pesticide used.
Despite the large number and varieties of insecticidal
plant lectins described (Table 1) the real allure of this ﬁeld
of research is the possibility of using plant lectins as potent
control agents to engineer crop plants for insect resistance
(Jouanin et al., 1998; Vaughan et al., 1999). Currently, the
two major groups of plant-derived genes used to confer
insect resistance on crops are those of inhibitors of digestive
enzymes (proteases and amylase inhibitors) and lectins
(Schuler et al., 1998). Several bioassay studies of lectin-
expressing plants, in particular GNA-containing, have been
reported recently (Hilder et al., 1995; Down et al., 1996;
Gatehouse et al., 1996; Czapla, 1997; Rao et al., 1998;
Foissac et al., 2000; Couty et al., 2001a). Overall, transgenic
plants expressing high levels of lectins exhibited some
degree of resistance to the target insect. It is worth
mentioning that the great interest on transgenic crop plants
expressing the gene for GNA or other mannose-binding
lectins such as ASA resides in the fact that although these
lectins show toxicity against species of various insect orders
they are non toxic to mammals and birds (Powell et al.,
1995; Down et al., 1996; Bandyopadhyay et al., 2001).
Therefore GNA has been transferred and expressed in
several crop plants (Table 2).
In parallel studies on the possible toxic or antinutritive
effects of lectins, being considered for introduction into
transgenic crops, on parasitoids of insect pests have been
carried out to evaluate the ecological problems that such
transgenic plants could bring to dependent secondary
species or symbiotes in the ﬁeld (Bell et al., 1999, 2001;
Down et al., 2000; Couty et al., 2001bc; Tomov and Bernal,
2003). Fortunately, the studies conducted so far with this
purpose have demonstrated that the effects of lectins on
parasitoids are not acute. For example, no acute toxicity of
GNA-containing aphid towards its parasitoid two-spot
ladybird (Adalia bipunctata L.; Coleoptera: Coccinellidae)
larvae fed on Myzus persicae (Homoptera: Aphididae) was
observed, although there were small effects on development
which led the authors to hypothesise that dietary GNA had
reduced the nutritive quality of the aphids thereby limiting
subsequent nutrient intake by the ladybirds and slowing
their development (Down et al., 2000). The results obtained
by Couty et al. (2001b) indicated that GNA delivered via
artiﬁcial diet to M. persicae was transferred to its parasitoid
Aphidius ervi (Hymenoptera: Aphidiidae) and that the
parasitoid larvae excreted most of the ingested GNA in
the meconium. Tomov and Bernal (2003) concluded that
although GNA transgenic sugarcane, ingested via Eoreuma
loftini tissues, was not acutely toxic to Parallorhogas
pyralophagus (Hymenoptera: Braconidae), sublethal effects
on life history parameters occurred both in the ﬁrst and
second generation of the parasitoid. These effects might be
considered in a broader context to determine their possible
Lectins are highly antinutritional and/or toxic substances
being detrimental to various plant-eating organisms. This
property is associated, in part, to their high resistance to
proteolysis in gastrointestinal tract of monogastric, rumi-
nants and insects, to their capacity of binding to epithelial
cells lining the small intestine and to their ability to
modulate intestinal and systemic metabolism. It has been
extensively demonstrated that plant lectins are effective
biological agents against insect attack. In fact, insect-
resistant plants produced by expression of lectin genes in
transgenic plants are already a reality. This approach could
increase crop productivity and reduce the usage of pesticide.
However, few lectins tested for this purpose have been
speciﬁcally selected on the basis that they convey high
resistance to disease or predators in plants, whilst simul-
taneously having a low toxicity to higher mammals,
including man. Hence, future research priority must be
given to ﬁnding other lectins with these above character-
istics hoping to draw deﬁnitive conclusions to two basic
questions: (a) What effects do lectins have in a diet? (b)
What effects do insect-resistant transgenic plants have when
pest and their parasitoids or symbiotes encounter them in the
This work was supported by Conselho Nacional de
´ﬁco e Tecnolo
´gico (CNPq), Pro-
grama de Apoio a Nu
´cleos de Excele
˜o de Aperfeic¸oamento de Pessoal de Nı
Superior (CAPES), Programa Nacional de Cooperac¸a
ˆmica (PROCAD) and Fundac¸a
Pesquisa do Estado do Ceara
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