ORIGINAL RESEARCH PAPER
Jet exhaust particles alter human dendritic cell maturation
D. Ferry•C. Rolland•D. Delhaye•F. Barlesi•
P. Robert•P. Bongrand•Joana Vitte
Received: 15 June 2010/Revised: 22 September 2010/Accepted: 22 September 2010/Published online: 12 October 2010
? Springer Basel AG 2010
Objective and design
pollutants, little is known about jet kerosene characteristics
Materials and methods
Particles yielded by experimental
kerosene combustion in a jet engine were characterizedwith
electron microscopy and X-ray energy dispersive spec-
troscopy. Immature human monocyte-derived dendritic
cells were exposed for 18 h to 10, 25 or 100 lg/mL jet
exhaust particles and/or Escherichia coli-derived endo-
toxin. Antigen-presenting and costimulation molecules
(HLA DR, CD40, CD80, CD86, CD11c), tumor necrosis
factor-a and interleukin-10 production were measured.
Among combustion-derived air
(9.9 nm), carbonaceous and exert an adjuvant effect on
human monocyte-derived dendritic cell maturation in vitro.
Concomitant particle and endotoxin stimulation induced a
high cytokine production with low antigen-presenting
molecules; particle contact prior to endotoxin contact led to
an opposite phenotype. Finally, low cytokine production
and high costimulation molecules were present when par-
ticle adjunction followed endotoxin contact.
Jet exhaust particles act as adjuvants to
endotoxin-induced dendritic cell maturation, suggesting
possible implications for human health and a role for the
time pattern of infectious and pollutant interplay.
The primary particles of jet exhaust are spherical
Ambient particulate matter ? Allergy
Jet exhaust ? Dendritic cell ? Air pollution ?
Responsible Editor: Michael Parnham.
Centre Interdisciplinaire de Nanoscience de Marseille CINaM
CNRS UPR 3118, Universite ´ Aix-Marseille 2, Campus de
Luminy, case 913, 13288 Marseille Cedex 9, France
C. Rolland ? P. Robert ? P. Bongrand ? J. Vitte
INSERM UMR 600/CNRS UMR 6212, Universite ´
Aix-Marseille 2, 13009 Marseille, France
Atmospheric Environment Unit, ONERA, 29 Avenue de la
Division Leclerc, 92320 Chatillon, France
Universite ´ Aix-Marseille 2, Po ˆle Cardiovasculaire et Thoracique,
Ho ˆpital Nord, Assistance Publique Ho ˆpitaux de Marseille,
Service d’Oncologie Multidisciplinaire et Innovations
The ´rapeutiques, Chemin des Bourrely, 13915 Marseille
Cedex 20, France
P. Robert ? P. Bongrand ? J. Vitte (&)
Laboratoire d’Immunologie, Ho ˆpital de la Conception,
Assistance Publique Ho ˆpitaux de Marseille, 147 boulevard
Baille, 13005 Marseille, France
e-mail: firstname.lastname@example.org; email@example.com
Inflamm. Res. (2011) 60:255–263
Author's personal copy
The effect of air pollution on the prevalence and severity of
pulmonary and cardiovascular diseases, including asthma
and cancer, is now well recognized, but its pathophysiol-
ogy remains unclear [1, 2]. Recent studies demonstrated
that current diesel exhaust levels in urban areas induce
small-airway effects resulting in a decline in lung function
[3, 4]. Both initiation and exacerbation of allergic asthma
may be related to air pollution levels [5, 6]. Aerosols,
defined as atmospheric particles in suspension, are mostly
of natural origin: sea salt, volcanic or desert dust. Particles
less than 10 lm in diameter enter lower airways and affect
local homeostasy and immune responses. In urban areas,
15% of the respirable particulate matter that is 10 lm or
less (PM10) originates from diesel vehicle exhaust, and this
proportion reaches 45% when particles smaller than
0.1 lm are considered . Dendritic cells (DC) play a
crucial role in sampling airway particles and locally initi-
ating either an immune response or tolerance [8, 9]. Diesel
exhaust particles (DEP), including the fine (\2.5 lm,
PM2.5) and ultrafine (\0.1 lm, PM0.1) fractions, induce
maturation of DC through multiple pathways including
granulocyte-monocyte colony-stimulating factor (GM–
CSF) . In a murine model, inhalation of DEP in the
presence of lipopolysaccharide (LPS) increases lung pro-
duction of the proinflammatory cytokine tumor necrosis
factor-a (TNF-a) . The biological fraction of inhaled
particulate matter has been reported to play an important
role in airway phagocyte activity [1, 6]. Unlike DEP, which
are now being studied in vitro and in vivo, the residue of air
traffic combustion and pollution has received little atten-
tion. Yet, aircraft-derived pollution is remarkable by its
geographical dispersion (it is not confined to urban areas)
and also by direct injection into the troposphere and low
stratosphere. Jet exhaust particles (JEP), therefore, persist
for a long time in the atmosphere and can exert their effects
on climate and health for an extended period (Inter-
governmental Panel on Climate Change, 2007). Little is
known about the interaction of JEP with the respiratory
system or about their ability to adsorb pollens, bacteria or
fungi and convey these to airway phagocytes.
We therefore collected JEP emitted from aircraft engines
that are largely used within the world fleet. Physico-
chemical properties of the particles were assessed before
testing their biological effects on monocyte-derived DC in
vitro, with and without DC maturation by LPS. JEP alter
DC maturation, as reflected by costimulatory molecules
acquisition and cytokine production. Moreover, the DC
maturation pattern differs according to the time pattern of
JEP–LPS adjunction. These results suggest JEP involve-
ment in the onset and maintenance of lung inflammation
and allergic responses.
Materials and methods
Blood (20 mL) was taken by veinpuncture from 27 healthy
donors (20 men and 7 women, mean age 53 ± 15 years,
25–80). All subjects had been informed about the nature
and purpose of the study and had provided written consent
before enrolment. The study had been approved by the
local ethics committee.
JEP are carbonaceous compounds resulting from kerosene
combustion in aircraft turbofan engines. JEP sampling was
made on a civil aero-engine bench during take-off/landing
cycles. Particles were collected by direct impaction on
polycarbonate membranes (Nucleopore?, Isopore), silicon
windows (UQG Ltd, Cambridge), and electron microscope
grids (Holey carbon film, Oxford Instruments) that were
located in the exhaust flow axis at 27 m behind a CFM56
commercial aircraft engine. Physico-chemical analyses
were performed by scanning electron microscopy, trans-
mission electron microscopy, and X-ray energy dispersive
spectroscopy (XREDS). For cell culture experiments, JEP
were solubilized in dimethylsulfoxide at a final concen-
tration of 50 mg/mL and stored at ?4?C.
Cell culture reagents
Cell culture reagents were from Invitrogen unless otherwise
specified. Cells were cultured in RPMI 1640 supplemented
with 10% fetal bovine serum, 2 mM L-glutamin, 100 U/mL
penicillin and 100 lg/mL streptomycin. Recombinant
human GM–CSF was purchased from RnDSystems and
recombinant human interleukin-4 (IL-4) from AbCys. Low
endotoxin specifications were given for all cell culture
reagents. E. coli O55:B5 LPS was from Sigma–Aldrich.
DC were issued from in vitro differentiation of circulating
monocytes. Briefly, fresh heparinized blood was used for
leukocyte separation (MSL, Eurobio), then peripheral
blood mononuclear cells were allowed to adhere for 1.5 h
to cell culture plates (Dutscher). Non-adherent cells were
removed and monocytes were cultured for 7 days.
Recombinant human IL-4 (300 U/mL) and GM–CSF
(100 U/mL) were added at the onset of cultures and every
other day. On the sixth day, non-adherent immature DC
were harvested, counted, transferred to 24-well plates
(Nunc) and used for maturation experiments as follows.
Standard DC maturation was induced with 1 lg/mL
256D. Ferry et al.
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endotoxin. JEP were added to DC cultures (a) on day 6, or
(b) on day 6 in conjunction with LPS, or (c) on day 6 after
LPS adjunction on day 5, or (d) on day 5 followed by
endotoxin adjunction on day 6. Thus, JEP effects were
tested on immature DC (settings a and d), on mature DC (c)
and on DC undergoing the maturation process (b). Three
JEP concentrations were tested: 100, 25, and 10 lg/mL,
following preliminary dose–response experiments on
monocytic THP-1 cells, then on human monocyte-derived
DC, showing no toxic effects with JEP concentrations of
100 lg/mL or less.
On day 7, DC supernatants were harvested and stored at
-80?C for cytokine determination, DC viability was
assessed by trypan blue exclusion, then DC were labeled
for flow cytometry.
Cultures of DC were stimulated as indicated above. On the
seventh day, supernatants were harvested and stored at
-80?C for further cytokine determination. Levels of TNF-a
and IL-10 in DC supernatants were measured using com-
mercial quantitative non-competitive sandwich ELISAs
(Quantikine, RnDSystems). For each patient, cytokine
production by mature DC was expressed as fold induction
of the corresponding immature DC cytokine production.
For DC exposed to both JEP and LPS, cytokine production
was expressed as fold induction of LPS-matured DC.
Fluorescently labeled mouse anti-human antibodies (HLA
DR, CD40, CD80, CD86) and isotype-matched control
antibodies were purchased from Beckman Coulter. CD11c-
FITC and its isotype-matched control antibody were from
DakoCytomation. After harvesting, DC were washed,
stained with test or control antibodies for 30 min in the
dark at room temperature, rinsed and resuspended in
phosphate-buffered saline containing 1% formaldehyde.
Flow cytometry experiments were performed with an Epics
XL (Beckman Coulter).
For each maturation condition of each donor, i.e.
immature DC or DC ? JEP or DC ? JEP ? LPS, the
fluorescence measurement of the isotypic control was
subtracted from measurements of all surface molecule
densities, in order to avoid possible artifacts due to particle
aggregates or particle autofluorescence.
The percentage of positive cells and the median fluores-
cence intensity for each surface molecule were then
Data are expressed as mean ± standard error of the mean.
Data sets were compared and tested for significance using
ANOVA, then Student’s t test. Statistical significance was
accepted for p\0.05.
Physical and chemical characterization of JEPs
The particulate matter emitted by the aircraft engine con-
sisted of small aggregates (Fig. 1a), with a mean gyration
diameter of 89 ± 4 nm. These aggregates were made of
primary particles (Fig. 1b) with geometries very similar to
spheres and a mean diameter of 9.9 ± 1.7 nm. Size distri-
butions of both aggregates and primary particles followed a
log-normal law. The complex geometry of JEP aggregates
to be 1.92 ± 0.05.
Fig. 1 Jet exhaust particle characterization: aggregates were col-
lected on a porous membrane (a, scanning electron micrograph);
primary particles were spherical and consisted of concentric layers (b,
transmission electron micrograph); turbostratic structure was demon-
strated through electron diffraction pattern of primary particles (c)
Jet exhaust particles alter human dendritic cell maturation 257
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In addition to their spherical morphology, primary JEP
exhibited an onion-like structure of concentric graphene
layers with a lateral extension of about 2–3 nm (Fig. 1b).
The electron diffraction patterns of these particles showed
the specular reflection and a set of diffuse rings, typical of
turbostratic structures, corresponding in this case to the
(002), (10), and (11) reflections (Fig. 1c). XREDS analyses
(98 ± 3%), with a few oxygen atoms (1.5 ± 0.4%) and
traces of sulfur (0.12 ± 0.05%, not shown).
When compared to DEP [12, 13], JEP proved similar in
terms of size range, elemental composition, turbostratic
structure, and fractal dimension values. Yet, primary JEP
diameter was smaller, ranging from one-third to half the
average DEP diameter (Table 1).
High combustion temperatures together with immediate
collection of JEP and further sterile handling avoided LPS
contamination of JEP samples. The absence of LPS con-
tamination of JEP was also checked with the measure of
CD83 expression on immature and JEP-exposed DC.
Indeed, CD83 upregulation is a sensitive detector of LPS
stimulation, even when minimal amounts of LPS are
Modulation of DC cytokine production
JEP concentrations of 100, 25, and 10 lg/mL were chosen,
according to previous studies on ambient particulate matter
 and to preliminary experiments in our laboratory that
had confirmed the absence of toxic effects of 100 lg/mL
JEP or less on monocytic and monocyte-derived DC cell
cultures (not shown). For each JEP concentration, kinetics
of the JEP-DC interaction was studied.
Immature DC produced very low levels of TNF-a and
IL-10, and adjunction of JEP alone resulted in a
nonsignificant elevation of both cytokines (Fig. 2a). As
expected, LPS maturation induced an approximate 500-
fold increase in TNF-a production and a 30-fold increase in
IL-10 production (Fig. 2a, p\10-7).
TNF-a production was further increased in DC simul-
taneously exposed to LPS and JEP, with higher JEP
concentrations being more efficient (Fig. 2b). Thus,
100 lg/mL JEP induced a twofold increase in TNF-a
production as compared with standard LPS-matured DC
(p = 3 9 10-5).
Table 1 Comparative analysis of jet and Diesel exhaust particles
Jet exhaustDiesel exhaust
9.9 ± 1.720–35
89 ± 4160–350
Fractal dimension1.92 ± 0.051.77 ± 0.14
Adsorbed moleculesPolycyclic aromatic
Exhaust particles collected from a commercial jet engine mounted on
a test bench were characterized through physico-chemical methods
and compared to data previously published with diesel exhaust par-
ticles [12, 13]
Fig. 2 Cytokine production by JEP-exposed DC compared to LPS-
matured DC and immature DC. JEP at 10, 25 or 100 lg/mL induced a
slight, nonsignificant increase in cytokine production as compared
with immature dendritic cells. Data for 25 lg/mL JEP are represented
here (a); concomitant JEP and LPS adjunction upregulated TNF-a and
IL-10 production in a dose-dependent fashion, while JEP adjunction
preceding or following LPS exerted opposite effects (b, c)
258 D. Ferry et al.
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On the contrary, JEP adjunction before or after LPS
maturation downregulated TNF-a production. Maximal
effect was seen with 25 lg/mL JEP adjunction following
LPS maturation, inducing a threefold decrease in TNF-a
production of DC (Fig. 2b, p\10-5).
IL-10 production showed a similar pattern of induc-
tion: simultaneous treatment of DC with LPS and JEP
resulted in an elevated IL-10 production, while other
experimental designs led to decreased levels of IL-10
(Fig. 2c). The lowest IL-10 production was noted with
LPS maturation following the adjunction of 100 lg/mL
JEP, resulting in a threefold decrease of IL-10 production
Thus, DC maturation was altered following the time
pattern of JEP adjunction: simultaneous JEP and LPS
maturation upregulated both cytokine production, while
JEP adjunction before or after LPS maturation downregu-
lated it. Changes in JEP concentration further influenced
Effect of JEP on immature DC phenotype
The absence of JEP toxicity was checked through trypan
blue exclusion from DC. The myeloid DC differentiation
molecule CD11c, which is not expressed by circulating
monocytes, was expressed by 96–100% of cells after a
6-day culture and remained stable thereafter. Immature
DC displayed weak expression of HLA DR and CD40.
Low levels of CD80 were expressed by 44% of immature
DC, while CD86 was detected on 57% of these cells
At any of the concentrations tested, JEP alone did not
induce DC maturation in an efficient manner, as reflected
by weak, nonsignificant increases in the percentage and/or
median fluorescence intensity of HLA DR, CD80 and
CD86-expressing DC (Fig. 3). JEP adjunction for 24 or
48 h prior to analysis yielded similar results. As expected,
LPS-induced maturation led to significant increases in
surface densities of HLA DR and CD40 and to the
recruitment of virtually all cells to CD80 and CD86-
expressing DC (Table 2 and Fig. 3, p\10-3).
Modulation of LPS-induced DC costimulatory pattern
JEP adjunction altered DC maturation, mainly through
changes in HLA DR and CD86 median fluorescence
Concomitant JEP and LPS maturation resulted in an
impaired acquisition of HLA DR expression: half the
median fluorescence intensity was measured at the surface
of this DC group as compared with standard LPS matura-
tion (Fig. 4a, p = 0.001).
On the contrary, HLA DR acquisition was stimulated by
JEP contact prior to LPS maturation, with a maximum of
39% increase in the median fluorescence intensity with
25 lg/mL JEP (p = 0.03). Finally, JEP adjunction after the
onset of LPS maturation was not associated with significant
changes in HLA DR median fluorescence, although a slight
increase was noted with 25 lg/mL JEP.
CD86 paralleled HLA DR in DC exposed concomitantly
to 10 or 25 lg/mL JEP plus LPS, showing a slight decrease
CD86 expression also decreased with JEP adjunction at
any concentration prior to LPS.
Finally, JEP adjunction after the onset of LPS matura-
tion was associated with an increase in CD86 median
Table 2 Percentage of dendritic cells staining positive for differentiation and maturation molecules
ImmatureJEP aloneLPS maturationConcomitant LPS ? JEPJEP before LPS LPS before JEP
CD11c98 96 97979596
HLA DR989797 9896 96
CD 409889 9696 9596
CD 80 44 5293* 83*82*89*
CD 865763 97* 91* 94*96*
Dendritic cell differentiation was assessed by CD11c staining. Antigen presentation is performed by HLA DR, related molecules and costi-
mulation markers such as CD40, CD80 and CD86, which are strongly upregulated on DC after maturation (*p\10-3). Data with JEP represent
the mean of three concentrations: 10, 25, and 100 lg/mL
Fig. 3 DC maturation induced by 25 lg/mL JEP as compared with
immature DC and LPS maturation. Mean fluorescence of surface
molecules was expressed in arbitrary fluorescence units. Significant
differences (p\0.05) between immature and LPS-matured DC are
indicated by asterisks
Jet exhaust particles alter human dendritic cell maturation259
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intensity. A concentration of 10 lg/mL JEP yielded a 62%
increase in CD86 expression.
Taken together, JEP modulation of surface molecule
acquisition or upregulation involved mainly HLA DR and
CD86 and showed less dose-dependent changes than did
Experimental patterns of DC maturation
Taken together, markers of DC maturation showed distinct
patterns, depending on LPS versus JEP experimental
scheme. Based on HLA DR and CD86 surface intensity and
TNF-a and IL-10 production, three patterns of DC matu-
ration were identified (Figs. 2, 4, 5). DC maturation under
concomitant LPS and JEP (25 or 100 lg/mL) stimulation
presented with abundant TNF-a and IL-10 production and
weak HLA DR expression, while CD86 remained stable.
Low TNF-a and IL-10, high HLA DR and low CD86 were
induced by JEP contact prior to LPS adjunction. Finally,
LPS prior to JEP treatment yielded similarly low cytokine
output, but stimulated HLA DR and CD86 expression.
These results show differential DC activation and thus
suggest that the time pattern of JEP adjunction may induce
distinct immune responses downstream.
Air traffic has been growing by 5% annually since 1990
 and the extended persistence of its waste in the
atmosphere prompted us to study the effect of aircraft
exhausts on human health. We collected JEP at the ground
Fig. 4 JEP time and dose-
dependent modulation of LPS
maturation. HLA DR surface
intensity was downregulated by
concomitant JEP and LPS
adjunction and upregulated by
JEP exposure prior to or
following LPS maturation (a).
CD86 intensity was higher
when JEP exposure had been
preceded by LPS, but lower in
the other experimental settings
(c). Significant differences
(p\0.05) from LPS-matured
DC are indicated by asterisks
260 D. Ferry et al.
Author's personal copy
level during experimental take-off/landing cycles of a civil
aircraft engine, established their physico-chemical proper-
ties and described alterations they induce in human
monocyte-derived DC maturation in vitro.
Primary JEP were spherical, with a mean diameter of
9.9 ± 1.7 nm. The complex geometry of JEP aggregates
could be described by their fractal dimension (Df=
1.92 ± 0.05), although they did not completely fulfil
requirements for fractals. However, the term has been
commonly used for many years to characterize fractal-like
particle geometry [16, 17]. JEP displayed physical, chem-
ical, and geometrical properties close to diesel exhaust
[12, 13]. Nevertheless, fractal structures of JEP were less
compact. This result indicates larger surfaces for small
molecule adsorption and, therefore, efficient shuttling of
allergens and/or carcinogens to lungs [7, 14]. Moreover, a
slightly smaller size of aircraft-derived elementary parti-
cles suggested higher deposition rate in tissues.
Final concentrations of 100 lg/mL JEP were active but
not toxic in our hands both on THP-1 cells and on human
monocyte-derived DC, consistent with studies on ambient
particulate matter . We chose human monocyte-
derived, GM–CSF and IL-4 driven DC as a model, because
these cells are closely related to myeloid, monocyte-
derived DC that replace lung resident DC in vivo in acute
conditions . We showed that JEP alone did not induce
DC maturation. Instead, JEP exert an adjuvant activity in
DC maturation. The ability of particulate matter to
induce DC maturation is a controversial issue. Lack of
direct particle effect on DC maturation was reported in
earlier studies with ambient particulate matter or diesel
exhaust particles, but also in a more recent paper using
standardized, spark generated elemental carbon-ultrafine
particles in a murine model of allergy and inhaled ultrafine
particles interaction . Some authors, therefore, con-
cluded that DEP displayed little, if any, biological activity
in murine and human models in the absence of a biological
stimulus, i.e. microbial components or allergenic challenge
[10, 11, 20]. Nevertheless, in other studies DEP were able
to induce DC maturation and an adaptive immune response
. This may be due to the experimental design allow-
ing epithelium-DC crosstalk (DEP instillation into mouse
airways leads to bronchial epithelial activation and sub-
sequent DC recruitment and maturation). Conversely, there
is major variability in DEP chemical and toxicological
properties . Finally, bacterial contamination of the
particulate matter is not often assessed, despite the extreme
sensitivity of DC to these stimuli.
On the contrary, the combined action of JEP and
endotoxin exerted potent effects on DC maturation. Cyto-
kine production was more sensitive to higher JEP
concentrations than surface molecule expression. More-
over, different experimental time patterns yielded distinct
Simultaneous JEP and LPS exposure induced DC to
produce high amounts of TNF-a and IL-10, low HLA DR
and stable CD86. TNF-a promotes neutrophilic responses
and stimulates DC migration to secondary lymph organs,
while IL-10 is the major cytokine involved in DC induction
of T regulatory responses. Surface density of class II
molecules including HLA DR modulate DC effectiveness
in antigen presentation to native and memory T cells. Thus,
simultaneous JEP and LPS activation, through high TNF-a
and IL-10 and low HLA DR should not favor an effector T
response, but rather a regulatory one.
In contrast, JEP exposure of immature DC (prior to LPS
activation) yielded mature DC with high levels of HLA DR
expression, low IL-10 production and low CD86 expres-
sion. CD86, a member of the B7 family of costimulation
molecules, participates in the regulation of the Th1/Th2
balance. On the other hand, CD86 and HLA DR were both
expressed at high levels by DC exposed to LPS prior to
JEP, along with a diminished TNF-a and IL-10 production.
Although the amplitude of changes does not exceed a
twofold induction, these results confirm and complete
recent studies. Indeed, IL-10 expression by antigen-pre-
endogenous IL-10 upregulation might contribute to allergic
inflammation [23, 24]. Selective upregulation of costimu-
latory molecules and altered production of IL-10 and
TNF-a have been associated with fungal allergen-induced
Th2 polarization of DC . Finally, IL-10 was unchanged
in bronchoalveolar fluid of sensitized mice exposed to
elemental carbon-ultrafine particles inhalation before
allergenic challenge .
Fig. 5 DC maturation patterns following combined JEP (25 or
100 lg/mL) and LPS maturation. Standard LPS maturation is
represented as a value of one and variations of TNF-a, IL-10, HLA
DR and CD86 expression are shown
Jet exhaust particles alter human dendritic cell maturation 261
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On the other hand, DEP have been shown to synergize
with LPS to increase inflammatory cell recruitment to the
lung and to upregulate local TNF-a production . In
vivo, native but not heat-inactivated ambient PM2.5–10
induce airway monocytes to produce TNF-a mRNA .
Highly polluted DEP shift maturation and functionality of
murine bone marrow-derived DC toward a Th2-polarized,
pro-allergic inflammation . The adjuvant effect of
ultrafine particles can also synergize with allergenic pro-
teins . Interestingly, in the paper by Alessandrini et al.
, early effects of ultrafine particles were analyzed at the
between slight but significant particle effects per se at the
molecular level (lung tissue peroxidation, lung NFjB
activation immediately after particle exposure) and the
fluid inflammatory infiltrates, lung functional tests or
later lung NFjB activation. Thus, LPS and other biologi-
cal molecules shuttled by airborne particles play decisive
roles in the activation of the lung mononuclear phagocyte
CD80 and CD86 are upregulated on myeloid DC in vivo
following carbon black particle plus ovalbumin intranasal
administration . CD80 and CD86 expression is asso-
ciated with T helper response decision. CD80 to CD86
ratio might reflect the ability of DC to induce Th1 rather
than Th2 immune responses. Although the Th1/Th2 para-
digm has evolved into a more complex picture including
Treg and Th17 responses [27, 28], its interplay with asthma
and allergy has not been fully depicted yet.
The time pattern of particle and infectious stimulation
seems to play a critical role. Concomitant exposure to
traffic-related particles and house-dust endotoxin had a
synergistic effect on persistent wheezing during childhood
. In ovalbumin-sensitized mice exposed to diesel
exhaust particles prior to influenza virus infection, lung
allergic inflammation was evidenced through eosinophil
recruitment, Th2-type cytokine production and the absence
of IL-10 induction .
In conclusion, we show here that JEP are physically,
chemically, and biologically related to, but different from,
DEP. They act as adjuvants, exerting little functional
effects on human immature DC expression of costimula-
tory molecules and cytokine production, but synergize with
LPS to induce distinct maturation patterns depending on
the time sequence of JEP and LPS activation. Further
investigations should provide insights into the mechanisms
of cellular alteration, particularly with respect to the gen-
eration of reactive oxygen species and help characterize
responses to JEP and DEP in the context of phenotypic,
secretory, T cell activation, and dendritic-bronchial epi-
Charvin for helpful discussions and assistance with formal issues and
Ms. Elisabeth Wostrowski and Ms. Dolores Migneret for technical
This work was supported by Assistance Publique Ho ˆpitaux de
Marseille, Institut National de la Sante ´ Et de la Recherche Me ´dicale,
Centre National de la Recherche Scientifique, and Universite ´ de la
Me ´diterrane ´e.
We thank Dr. Patrick Sudour and Dr. Nathalie
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