I Carlstedt

Lund University, Lund, Skåne, Sweden

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Publications (125)506.27 Total impact

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    ABSTRACT: Mucus is a highly hydrated uniquely structured gel that in conjunction with the ciliated cells in the surface epithelium forms the mucociliary clear­ance system essential for the protection of the respiratory tract [1]. The polymer matrix of the mucus biofilm is provided by very large complex glycoproteins that were formerly known as mucus glycoproteins but which are now commonly referred to as mucins [2-7]. Mucins are high-M„ extensively 0-linked glycoproteins of exceptional mass size and daunting complexity that are synthesised by cells in both the surface epithelium and in the underlying submucosal glands. In normal airways mucus production asthma, cystic fibrosis and chronic bronchitis, mucus hypersecretion may cause major problems in airway clearance, resulting in impaired gas exchange and bacterial colonisation leading to infection and lung damage. In this chapter we will focus on the large polymeric mucins that are responsible for the formation of the gel-like protective barrier in human airways.
    Airway Mucus: Basic Mechanisms and Clinical Perspectives, 07/2011: pages 19-39;
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    ABSTRACT: Cancer-associated alterations in cell surface and secreted glycoproteins have been catalogued for many years but many of the studies of alterations in mucin carbohydrate have relied on histochemical or immunohistochemical methods, with little direct chemical analysis. In this study, we analyzed the O-glycosylation pattern of MUC2 glycoprotein isolated from colorectal carcinomas, transitional mucosa and resection margins from three patients with blood group A, B and O, respectively. After alkaline borohydride treatment, the released oligosaccharides were structurally characterized by nanoESI Q-TOF tandem mass spectrometry without prior fractionation or derivatization. As expected, we found an increased expression of sialyl-Tn antigen in the colonic cancer mucins. A more interesting feature was the increased expression of a core 3 sialyl-Le(x) hexasaccharide, NeuAcalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3(NeuAcalpha2-6)GalNAc in tumor, which appeared to compete with its sulfo-Le(x) counterpart in normal tissue, SO3-3Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3(NeuAcalpha2-6)GalNAc. This antigen, whose structure was confirmed by NMR experiments, is based on a core 3 glycan and may be a potential marker for the malignant transformation of colonic cells. Unexpectedly, most of the glycans recovered in normal and carcinomas extracts were based on a sialylated core 3, GlcNAcbeta1-3(NeuAcalpha2-6)GalNAcol. Moreover, the pattern of glycosylation was very similar between mucins isolated from each sample, the main differences related to the level of expression of the major oligosaccharides. The data obtained in this investigation may have value for future screening studies on colorectal cancer.
    Journal of Proteome Research 02/2009; 8(2):702-11. DOI:10.1021/pr800740j · 4.25 Impact Factor
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    ABSTRACT: Transposition of intestinal segments is frequently used for bladder reconstruction. Following transposition, bowel segments continue to produce mucus and a correlation between excessive mucus production and complications such as urinary tract infection or catheter blockage has been observed for a long time. However, no information is currently available on the change of mucin expression and glycosylation under these abnormal conditions. In this study, the variable number tandem repeat region and the irregular repeat domain of human MUC2 were isolated as two glycopeptide populations after reduction and trypsin digestion followed by gel chromatography from urine of patients transposed with urinary bladders. After alkaline borohydride treatment, the oligosaccharides released from the whole MUC2 mucin and the two glycosylated domains were investigated by nanoESI Q-TOF MS/MS (electrospray ionization quadrupole time-of-flight tandem mass spectrometry). More than 60 different glycans were identified, mainly based on sialylated core 3 structures. Some core 1, 2 and 4 oligosaccharides were also found. Most of the structures were acidic with NeuAc residues mainly alpha2-6 linked to the N-acetylgalactosaminitol and sulphate residues exclusively 3-linked to galactose. No expression of blood group A and B or Sda/Cad determinants was observed. Similar patterns of glycosylation were found in the tandem repeat region and the irregular repeat domain and the level of expression of the major oligosaccharides were in the same order of magnitude. The most interesting feature of this study was that sialyl-Tn antigen, which is considered as a tumour antigen, was the oligosaccharide most highly expressed. This result suggests that mucins from intestinal transposed segments are abnormally glycosylated.
    Glycoconjugate Journal 05/2008; 25(3):213-24. DOI:10.1007/s10719-007-9079-3 · 2.52 Impact Factor
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    ABSTRACT: Goblet cells produce mainly MUC5AC, but also MUC5B and some MUC2 in apparently ‘irritated’ airways. MUC5B dominates in the submucosal glands although a little MUC5AC and MUC7 are usually present. MUC4 originates from the ciliated cells. After separation into a gel and a sol phase, lysozyme and lactoferrin are enriched in the salivary gel phase suggesting that mucus may act as a matrix for ‘protective’ proteins on the mucosal surface. A salivary MUC5B N-terminal fragment consistent with a cleavage event in the D′ domain was detected with antibodies against various N-terminal peptide sequences suggesting that assembly of MUC5B occurs through a mechanism similar to that of the von Willebrand factor. Identification of additional cleavage sites C-terminal to the D′ domain suggests that most of the N-terminal low-glycosylated part of MUC5B may be removed without affecting the oligomeric nature of the mucin. Possibly, the generation of mucins with different macromolecular properties through proteolytic ‘processing’ is one way of adapting the mucus polymer matrix to meet local physiological demands. Monomeric mucins that appear to turn over rapidly in the airway epithelium have been identified using radiolabelled mucin precursors. ‘Shedding’ of such mucins after microbe attachment may prevent colonization of epithelial surfaces.
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    ABSTRACT: Helicobacter pylori causes peptic ulcer disease and gastric cancer, and the oral cavity is likely to serve as a reservoir for this pathogen. We investigated the binding of H. pylori to the mucins covering the mucosal surfaces in the niches along the oral to gastric infection route and during gastric disease and modeled the outcome of these interactions. A panel of seven H. pylori strains with defined binding properties was used to identify binding to human mucins from saliva, gastric juice, cardia, corpus, and antrum of healthy stomachs and of stomachs affected by gastritis at pH 7.4 and 3.0 using a microtiter-based method. H. pylori binding to mucins differed substantially with the anatomic site, mucin type, pH, gastritis status, and H. pylori strain all having effect on binding. Mucins from saliva and gastric juice displayed the most diverse binding patterns, involving four modes of H. pylori adhesion and the MUC5B, MUC7, and MUC5AC mucins as well as the salivary agglutinin. Binding occurred via the blood-group antigen-binding adhesin (BabA), the sialic acid-binding adhesin (SabA), a charge/low pH-dependent mechanism, and a novel saliva-binding adhesin. In the healthy gastric mucus layer only BabA and acid/charge affect binding to the mucins, whereas in gastritis, the BabA/Le(b)-dependent binding to MUC5AC remained, and SabA and low pH binding increased. The four H. pylori adhesion modes binding to mucins are likely to play different roles during colonization of the oral to gastric niches and during long-term infection.
    Helicobacter 05/2008; 13(2):81-93. DOI:10.1111/j.1523-5378.2008.00587.x · 4.11 Impact Factor
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    ABSTRACT: Author Summary The common ABO blood group antigen system was described in the early 20th century. In addition, it has been known for 60 years that the majority of individuals also express the corresponding ABO antigens (carbohydrate identity tags) in their saliva, tears, milk, and mucus secretions in the digestive tract. To this date, however, the biological function of the ABO blood group antigens has remained an enigma. Here, we show that the great majority of Rhesus monkeys are of blood group B and weak-secretors, i.e., are similar to the human populations in South Asia from where these monkeys originate. This observation suggests that an evolutionary adaptation in digestive tract mucosal carbohydrate patterns to local environmental selection has occurred. In addition, we demonstrate that long-term infection by the “peptic ulcer bacterium” Helicobacter pylori induces mucosal carbohydrate patterns that change according to the individual secretor phenotype. The common weak-secretor monkeys were apparently “protected,” as they had stable glycosylation, lower inflammation, and lower bacterial infection load, whereas the less common secretor animals had increased levels of inflammation-associated mucosal carbohydrate patterns and a transient decrease in the ABO blood group system type of carbohydrates. These novel observations suggest that the individual ABO blood group and secretor phenotype are part of human and non-human primate innate immunity against infectious disease.
    PLoS Pathogens 02/2008; 4(1):e2. DOI:10.1371/journal.ppat.0040002 · 7.56 Impact Factor
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    ABSTRACT: The gel-forming MUC5AC and MUC5B mucins have been identified as major components of human airway mucus but it is not known whether additional mucin species, possibly with other functions, are also present. MUC16 mucin is a well-known serum marker for ovarian cancer, but the molecule has also been found on the ocular surface and in cervical secretions suggesting that it may play a role on the normal mucosal surface. In this investigation, the LUM16-2 antiserum (raised against a sequence in the N-terminal repeat domain) recognized MUC16 in goblet and submucosal gland mucous cells as well as on the epithelial surface of human tracheal tissue suggesting that the mucin originates from secretory cells. MUC16 mucin was present in 'normal' respiratory tract mucus as well as in secretions from normal human bronchial epithelial (NHBE) cells. MUC16 from NHBE cells was a high-molecular-mass, monomeric mucin which gave rise to large glycopeptides after proteolysis. N- and C-terminal fragments of the molecule were separated on gel electrophoresis showing that the MUC16 apoprotein undergoes a cleavage between these domains, possibly in the SEA domain as demonstrated for other transmembrane mucins; MUC1 and MUC3. After metabolic labeling of NHBE cells, most of the secreted monomeric, high-molecular-mass [(35)S]sulphate-labelled molecules were immunoprecipitated with the OC125 antibody indicating that MUC16 is the major [(35)S]sulphate-labelled mucin in NHBE cell secretions.
    The International Journal of Biochemistry & Cell Biology 02/2007; 39(10):1943-54. DOI:10.1016/j.biocel.2007.05.013 · 4.05 Impact Factor
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    Sara Lindén · Jafar Mahdavi · Jan Hedenbro · Thomas Borén · Ingemar Carlstedt
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    ABSTRACT: Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer. The microbe is found in the gastric mucus layer where a pH gradient ranging from acidic in the lumen to neutral at the cell surface is maintained. The aim of the present study was to investigate the effects of pH on H. pylori binding to gastric mucins from healthy individuals. At pH 3, all strains bound to the most charged MUC5AC glycoform and to a putative mucin of higher charge and larger size than subunits of MUC5AC and MUC6, irrespective of host blood-group. In contrast, at pH 7.4 only Le(b)-binding BabA-positive strains bound to Le(b)-positive MUC5AC and to smaller mucin-like molecules, including MUC1. H. pylori binding to the latter component(s) seems to occur via the H-type-1 structure. All strains bound to a proteoglycan containing chondroitin sulphate/dermatan sulphate side chains at acidic pH, whereas binding to secreted MUC5AC and putative membrane-bound strains occurred both at neutral and acidic pH. The binding properties at acidic pH are thus common to all H. pylori strains, whereas mucin binding at neutral pH occurs via the bacterial BabA adhesin and the Le(b) antigen/related structures on the glycoprotein. Our work shows that microbe binding to membrane-bound mucins must be considered in H. pylori colonization, and the potential of these glycoproteins to participate in signalling events implies that microbe binding to such structures may initiate signal transduction over the epithelial layer. Competition between microbe binding to membrane-bound and secreted mucins is therefore an important aspect of host-microbe interaction.
    Biochemical Journal 01/2005; 384(Pt 2):263-70. DOI:10.1042/BJ20040402 · 4.40 Impact Factor
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    ABSTRACT: To study the expression of mucins in peripheral airways in patients with chronic obstructive pulmonary disease (COPD). Peripheral lung sections from smokers with COPD (n = 9) and age-matched controls including smokers (n = 11) and lifelong non-smokers with normal lung function (n = 6) were stained with alcian blue, periodic acid-Schiff (PAS) and by immunohistochemistry of mucins (MUC): MUC2, MUC4, MUC5AC, MUC5B and MUC6. Histochemical staining and immunoreactivity of bronchiolar epithelium were graded and the presence or absence of stained mucus in the bronchiolar lumen was evaluated. There were no differences in alcian blue and PAS epithelial staining between the three groups. Intraluminal PAS staining was significantly more frequent among COPD subjects (P < 0.05). The expression of MUC5AC was significantly higher in the bronchiolar epithelium of patients with COPD (P < 0.05). Within the bronchiolar lumen, the predominant mucin was MUC5B. Intraluminal MUC5B was significantly more frequent among COPD patients (P < 0.05). COPD is specifically associated with increased expression of MUC5B in the bronchiolar lumen and of the mucin MUC5AC in the bronchiolar epithelium. These changes in mucin production in the peripheral airways may contribute to the pathophysiology of COPD.
    Histopathology 12/2004; 45(5):477-84. DOI:10.1111/j.1365-2559.2004.01952.x · 3.45 Impact Factor
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    ABSTRACT: Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
    Science 08/2004; 305(5683):519-22. DOI:10.1126/science.1098801 · 33.61 Impact Factor
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    Sara Lindén · Thomas Borén · André Dubois · Ingemar Carlstedt
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    ABSTRACT: Mucins isolated from the stomach of Rhesus monkey are oligomeric glycoproteins with a similar mass, density, glycoform profile and tissue localization as human MUC5AC and MUC6. Antibodies raised against the human mucins recognize those from monkey, which thus appear to be orthologous to those from human beings. Rhesus monkey muc5ac and muc6 are produced by the gastric-surface epithelium and glands respectively, and occur as three distinct glycoforms. The mucins are substituted with the histo blood-group antigens B, Le(a) (Lewis a), Le(b), Le(x), Le(y), H-type-2, the Tn-antigen, the T-antigen, the sialyl-Le(x) and sialyl-Le(a) structures, and the expression of these determinants varies between individuals. At neutral pH, Helicobacter pylori strains expressing BabA (blood-group antigen-binding adhesin) bind Rhesus monkey gastric mucins via the Le(b) or H-type-1 structures, apparently on muc5ac, as well as on a smaller putative mucin, and binding is inhibited by Le(b) or H-type-1 conjugates. A SabA (sialic acid-binding adhesin)-positive H. pylori mutant binds to sialyl-Le(x)-positive mucins to a smaller extent compared with the BabA-positive strains. At acidic pH, the microbe binds to mucins substituted by sialylated structures such as sialyl-Le(x) and sialylated type-2 core, and this binding is inhibited by DNA and dextran sulphate. Thus mucin- H. pylori binding occurs via at least three different mechanisms: (1) BabA-dependent binding to Le(b) and related structures, (2) SabA-dependent binding to sialyl-Le(x) and (3) binding through a charge-mediated mechanism to sialylated structures at low pH values.
    Biochemical Journal 06/2004; 379(Pt 3):765-75. DOI:10.1042/BJ20031557 · 4.40 Impact Factor
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    ABSTRACT: The separation and characterization of salivary mucins is not straightforward because of their large size, heterogeneity, and molecular interactions. The MUC5B and MUC7 mucins are major glycoprotein components of saliva that are thought to play a vital role in maintaining oral health. MUC5B is also a major component of respiratory mucus and is produced by the tracheal and bronchial glands, while MUC7 has a more limited pattern of expression in the bronchial tree. MUC5B is a gel-forming mucin and thus confers viscosity, whereas MUC7 is much smaller. MUC7 has anti-fungal activity, and both mucins interact with bacteria. The aim of this work was to produce new monoclonal antibodies that can be used to quantify and characterize these mucins by standard laboratory procedures. Peptide sequences in non-conserved and non-glycosylated regions were selected and monoclonal antibodies produced by an efficient immunization and cloning strategy, and screening against purified mucins. Three new antibodies-EU-MUC5Ba and EU-MUC5Bb (against MUC5B) and EU-MUC7a (against MUC7)-were isolated that do not show cross-reactivity with other gel-forming mucins. All work on immunohistochemistry can be used for semi-quantitative immunoblotting after agarose gel electrophoresis. These reagents are valuable tools to study changes in these mucins in oral and respiratory disease, and unlike other monoclonal antibodies to these mucins they recognize epitopes that are not affected by glycosylation.
    Hybridoma and Hybridomics 11/2003; 22(5):293-9. DOI:10.1089/153685903322538818
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    ABSTRACT: A GC/MS procedure was developed for the analysis of all major constituents of glycoproteins. The rationale for this approach is that by using GC/MS analysis of the constituents as heptafluorobutyrate derivatives, it was possible to quantitatively determine the sialic acid, monosaccharide, fatty acids (when present), and the amino acid composition with the sample remaining in the same reaction vessel during the entire procedure. A mild acid hydrolysis was used to liberate sialic acids and was followed by formation of methyl-esters of heptafluorobutyrate (HFB) derivatives. After GC/MS analysis of sialic acids, the remaining material was submitted to acid-catalyzed methanolysis followed by the formation of HFB derivatives. After GC/MS analysis of the monosaccharides, the sample was supplemented with norleucine (as internal standard) and hydrolyzed with 6 M HCl followed by the formation of isoamyl-esters of HFB derivatives and GC/MS analysis. His and Trp residues were modified during the step of acid-catalyzed methanolysis, but the resulting derivatives were stable during acid hydrolysis and quantitatively recovered by GC/MS analysis. As a result, all constituents of glycoproteins (sialic acids, monosaccharides (or di- and trisaccharides) and amino acids) are identified in the electron impact mode of ionization and quantified using three GC/MS analysis in the same chromatographic conditions and using a limited number of reagents, a considerable advantage over previous techniques. This method is very sensitive, all data (qualitative and quantitative) being obtained at the sub-nanomolar level of initial material.
    Biochemistry 08/2003; 42(27):8342-53. DOI:10.1021/bi034250e · 3.02 Impact Factor
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    ABSTRACT: Gastric intestinal metaplasia (IM) and gastric cancer are associated with Helicobacter pylori, but the bacterium often is undetectable in these lesions. To unravel this apparent paradox, IM, H. pylori presence, and the expression of H. pylori virulence genes were quantified concurrently using histologic testing, in situ hybridization, and immunohistochemistry. H. pylori was detected inside metaplastic, dysplastic, and neoplastic epithelial cells, and cagA and babA2 expression was colocalized. Importantly, expression of cagA was significantly higher in patients with IM and adenocarcinoma than in control subjects. The preneoplastic "acidic" MUC2 mucin was detected only in the presence of H. pylori, and MUC2 expression was higher in patients with IM, dysplasia, and cancer. These novel findings are compatible with the hypothesis that all stages of gastric carcinogenesis are fostered by persistent intracellular expression of H. pylori virulence genes, especially cagA inside MUC2-producing precancerous gastric cells and pleomorphic cancer cells.
    The Journal of Infectious Diseases 05/2003; 187(8):1165-77. DOI:10.1086/368133 · 6.00 Impact Factor
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    ABSTRACT: The upper respiratory tract is involved in many acute and chronic respiratory tract diseases that present with the symptom of mucus hypersecretion. Mucin genes that encode for the backbone of glycoproteins contribute to the viscoelastic property of airway mucus. We examined the cellular expression and distribution of two major respiratory mucus-forming glycoproteins, MUC5AC and MUC5B, in normal human nasal tissues. Immunohistochemical analysis using polyclonal antibodies against the mucins MUC5AC and MUC5B was performed in normal human nasal tissues. An abundant staining of submucosal mucus gland and epithelial goblet cells for MUC5B was found. Immunohistochemical analysis of MUC5AC showed staining of surface epithelium goblet cells, whereas there was no staining of glandular cells. Comparison of the expression to lower airways revealed a similar pattern of expression of both mucins. The data in the present study demonstrated the localization of the two major respiratory mucin proteins in human nasal mucosa with a similar distribution of expression of MUC5AC and MUC5B in normal upper and lower airways. Mucin protein expression parallels that of mucin messenger RNA expression.
    The Laryngoscope 04/2003; 113(3):520-4. DOI:10.1097/00005537-200303000-00023 · 2.14 Impact Factor
  • Gastroenterology 04/2003; 124(4). DOI:10.1016/S0016-5085(03)82976-1 · 16.72 Impact Factor
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    ABSTRACT: We have studied the biosynthesis of mucins in organ cultures of human colon using isopycnic density-gradient centrifugation following pulse labelling with [(35)S]sulphate and [(3)H]-D-glucosamine. A high-density [(35)S]sulphate labelled component, of larger size than MUC2 monomers, appeared in the tissue and also in the medium. It was not degraded by reduction, trypsin digestion, digestion with chondroitin ABC lyase or heparan sulphate III lyase, but was cleaved into smaller fragments following alkaline borohydride treatment and appears to be a monomeric, mucin-like molecule containing a protease-resistant domain with a larger hydrodynamic volume than MUC2 monomers. Although this macromolecule incorporated much more radiolabel than MUC2, it was not detected using chemical analysis and thus appears to be a component with a high metabolic turnover present in a very small amount. Most of the [(3)H]-D-glucosamine label was associated with low-density material that was well separated from MUC2, which was poorly labelled. Most of MUC2 was associated with the tissue as an 'insoluble' complex. The amount of MUC2 remained constant and its associated radiolabel increased only slightly with time. Analysis of the MUC2 subunits from the reduced 'insoluble' complex showed the typical reduction-insensitive oligomers and confirmed that the radiolabel was associated with this mucin. The large size of the [(35)S]-labelled putative monomeric mucin makes it difficult to separate it from reduced insoluble complex MUC2. As a result, many studies of intestinal mucin synthesis and secretion in the past have most likely been performed on 'mixtures' of this mucin and MUC2 and are thus not possible to interpret as the metabolic behaviour of oligomeric mucins.
    Biochimie 03/2003; 85(3-4):381-90. DOI:10.1016/S0300-9084(03)00064-6 · 2.96 Impact Factor
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    ABSTRACT: In the stomach, Helicobacter pylori is found both in the mucus layer and adhering to the gastric epithelium. The aim of this study is to characterize the binding of H. pylori to human gastric mucins. H. pylori strains that bind the Lewis(b) (Le(b)) structure (via the BabA adhesin) and/or sialylated structures, along with isogenic adhesion deletion mutants, were used to identify microbe-binding mucins. Gastric mucins from 5 healthy individuals, isolated by density-gradient centrifugation, were investigated for H. pylori binding at neutral pH using a microtiter-based technique. H. pylori strains that express the BabA adhesins were shown to bind to the MUC5AC mucin in individuals expressing the Le(b) antigen. Further fractionation with an ion-exchange chromatography revealed Le(b)-positive MUC5AC glycoforms that differed in their receptor properties for different H. pylori strains. None of the H. pylori strains studied bound to mucins from Le(b)-negative individuals. However, all strains bound to low-density, nonmucin, Le(b)-negative material on top of the gradients. Binding of H. pylori to human gastric MUC5AC isolated from healthy individuals is BabA dependent and mediated by the Le(b) structure presented by the mucin. However, the BabA adhesins demonstrate strain-dependent preference in binding to MUC5AC glycoforms substituted with Le(b), allowing for great interindividual variability in host-microbe interactions.
    Gastroenterology 01/2003; 123(6):1923-30. DOI:10.1053/gast.2002.37076 · 16.72 Impact Factor
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    ABSTRACT: Gastric MUC5AC and MUC6 mucins were studied using polyclonal antibodies. Immunohistochemistry showed MUC5AC to originate from the surface epithelium, whereas MUC6 was produced by the glands. Mucins from the surface epithelium or glands of corpus and antrum were purified using CsCl/4M guanidinium chloride density-gradient centrifugation. MUC5AC appeared as two distinct populations at 1.4 and 1.3 g/ml, whereas MUC6, which was enriched in the gland tissue, appeared at 1.45 g/ml. Reactivity with antibodies against the Le(b) structure (where Le represents the Lewis antigen) followed the MUC5AC distribution, whereas antibodies against the Le(y) structure and reactivity with the GlcNAc-selective Solanum tuberosum lectin coincided with MUC6, suggesting that the two mucins are glycosylated differently. Rate-zonal centrifugation of whole mucins and reduced subunits showed that both gastric MUC5AC and MUC6 are oligomeric glycoproteins composed of disulphide-bond linked subunits and that oligomeric MUC5AC was apparently smaller than MUC6. A heterogeneous population of 'low-density' MUC5AC mucins, which were smaller than the 'high-density' ones both before and after reduction, reacted with an antibody against a variable number tandem repeat sequence within MUC5AC, suggesting that they represent precursor forms of this mucin. Following ion-exchange HPLC, both MUC5AC and MUC6 appeared as several distinct populations, probably corresponding to 'glycoforms' of the mucins, the most highly charged of which were found in the gland tissue.
    Biochemical Journal 06/2002; 364(Pt 1):191-200. DOI:10.1042/bj3640191 · 4.40 Impact Factor
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    ABSTRACT: Salivary mucins are known to play important roles in the formation of oral salivary films. The aims of the present study were to investigate the behaviour of salivary mucins at solid surfaces with different wettabilities, as well as the influence of electrolyte on the adsorption behaviour. A pure preparation of human salivary MUC5B was used together with a commercial one of bovine submaxillary mucin (BSM). Amounts adsorbed from freshly prepared solutions onto hydrophilic and hydrophobic surfaces versus time were measured in situ by ellipsometry. At low concentrations, larger amounts were adsorbed onto hydrophobic than onto hydrophilic silica indicating a higher affinity for the former surfaces. Furthermore, on hydrophilic surfaces adsorbed amounts of MUC5B and BSM show good agreement at low concentrations (<0.10 mg ml−1). However, at higher concentrations MUC5B adsorbed to a lower extent than BSM. At hydrophobic surfaces, isotherm shapes were similar for the two preparations, but the amounts were shifted to higher values for MUC5B. Finally, the presence of electrolyte increased adsorption and the increase was more pronounced on hydrophilic surfaces. The increased adsorption at a higher ionic strength indicates a more compact structure of the mucin due to electrostatic screening and the fact that the effect was more pronounced on the hydrophilic surfaces points to a higher relative importance of electrostatic interactions in this case. We conclude that the two mucins investigated behave in a qualitatively similar manner and show the highest affinity for hydrophobic surfaces.
    Colloids and surfaces B: Biointerfaces 06/2002; 25(2-25):139-146. DOI:10.1016/S0927-7765(01)00300-9 · 4.15 Impact Factor

Publication Stats

4k Citations
506.27 Total Impact Points


  • 1974–2011
    • Lund University
      • • Department of Experimental Medical Science
      • • Department of Surgery
      • • Department of Obstetrics and Gynecology
      • • Department of Biophysical Chemistry
      • • Department of Physical Chemistry
      Lund, Skåne, Sweden
  • 2008
    • Uniformed Services University of the Health Sciences
      • Department of Medicine
      베서스다, Maryland, United States
  • 2005
    • Umeå University
      • Department of Odontology
      Umeå, Västerbotten, Sweden
  • 1990–1996
    • The University of Manchester
      • Wellcome Trust Centre for Cell-Matrix Research
      Manchester, ENG, United Kingdom
  • 1993–1994
    • University of Gothenburg
      • Department of Medical Biochemistry and Cell Biology
      Goeteborg, Västra Götaland, Sweden
  • 1990–1993
    • Uppsala University
      • Department of Pharmacy
      Uppsala, Uppsala, Sweden
  • 1991
    • New York State
      New York City, New York, United States
    • St. George's School
      • Department of Physiology
      Middletown, Rhode Island, United States
  • 1989
    • Swedish University of Agricultural Sciences
      Uppsala, Uppsala, Sweden
  • 1984–1986
    • Lancaster University
      • Division of Biomedical and Life Sciences (BLS)
      Lancaster, England, United Kingdom