Sulfated glycans on oral mucin as receptors for Helicobacter pylori

Veerman, E.C.I.; Bank, Christine M C; Namavar, F.; Appelmelk, Ben J.; Bolscher, Jan G. M.; Amerongen, A. van Nieuw

doi:10.1093/glycob/7.6.737

Cited by 80 publications

(55 citation statements)

References 30 publications

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“…22 Furthermore, the rheological measurements in this study were accurate, made using large flexible macromolecules such as mucins, and their concentrations were calculated correctly. 17 The accuracy of the salivaryflow rates based on the gauze weight method, however, may be reduced by salivary density changes after administration of BoNT-A. The effect of these changes on the gauze weight method have not been investigated.…”

Section: Discussionmentioning

confidence: 99%

“…The total mucin concentration (U ⁄ mL) in thawed saliva was analysed using an enzyme-linked immunosorbent assay (ELISA) with mAb F 2 , as described previously. 17 Briefly, isolated mucins were 2-fold serially diluted in 0.1M NaHCO 3 (pH 9.6) starting from 2lg ⁄ mL and incubated overnight at 4°C in polystyrene wells of microtitre plates. After rinsing, mAb F 2 (approximately 1lg ⁄ mL) was added and the samples were incubated for 1 hour at 37°C.…”

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confidence: 99%

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Thickened saliva after effective management of drooling with botulinum toxin A

Erasmus

Hulst

Hoogen

et al. 2010

Develop Med Child Neuro

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AIM The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections.METHOD We enrolled 15 children (11 males and six females; age range 3-17y, mean age 9y 10mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function Classification System level IV or V; and two children with intellectual disability (IQ <70) who experienced moderate to severe drooling. Salivary flow rate and drooling quotient were measured at baseline and at different times after BoNT-A injections up to 24 weeks. The mucin concentration of saliva was analysed before and after BoNT-A treatment.RESULTS Both submandibular salivary flow rate (baseline 0.38mL ⁄ min; 24wks after injection 0.26mL ⁄ min) and drooling quotient (baseline 42.5%; 24wks 28.80%) were substantially reduced, with a concomitant increase in mucin concentration within 8 weeks after BoNT-A injection (from 0.612 to 1.830U ⁄ mL). The parents of nine children observed thickened saliva. Swallowing and chewing were problematic in seven children. Two of these children needed treatment with mucolytics because of pooling of thickened saliva in the throat. INTERPRETATIONWhen making decisions about the use of BoNT-A, the risk of problems with masticatory and swallowing functions as a result of thickening of saliva after BoNT-A treatment should be taken into account.Local injection of botulinum toxin type A (BoNT-A) into the salivary glands is used to prevent drooling. BoNT-A causes a temporary inhibition of SNAP-25, the presynaptic acetylcholine exocytotic synaptosome-associated protein which has a molecular weight of 25kDa. As a result, the gland's capacity to secrete water is depressed. After BoNT-A injection, basal saliva secretion is usually sufficient to moisten the oral cavity and to facilitate swallowing of food. Incidental side-effects have been reported, such as flu-like symptoms lasting for less than 2 days, swallowing difficulties, viscous saliva and dryness of the mouth, transient slight weakness of the masseter muscle or mouth openers, and, rarely, jaw dislocation. [1][2][3][4][5][6] Human saliva serves multiple functions in the oral cavity, including moistening of food, facilitation of mastication and swallowing, and cleaning and lubrication of the oral mucosa. 7 The seromucous sublingual, submandibular, and palatine glands secrete mucins that coat and protect the epithelial tissue of the oral cavity and give the typical viscoelastic character to saliva. Salivary mucins are primarily wetting agents that play a role in lubricating the tissue-environmental interface to reduce friction. 8,9 We have observed that in some children the saliva becomes sticky after intraglandular botulinum toxin injection and postulated that sticky saliva may cause swallowing problems as a result of an increase in protein concentrations and hence salivary viscosity, resulting in greater friction. 10 Previous studies have focused on the effect of BoNT-A on salivary proteins such as se...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Thickened saliva after effective management of drooling with botulinum toxin A

Erasmus

Hulst

Hoogen

et al. 2010

Develop Med Child Neuro

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“…However, the relative importance of each in colonization and/or pathogenesis has not been established. Among the host cell structures to which H. pylori have been shown to bind include sialic acids, fucose-containing blood group Ags, membrane lipids, mucin, and several basement membrane constituents (11)(12)(13)(14)(15)(16)(17). However, most of the studies to date appear to be complicated by differences in the model systems, strains used, and some apparent contradictions.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the bacterial structures responsible for adhesion and stimulation of host cell death may be regarded as important virulence factors. Although a number of epithelial cell molecules have been reported to contribute to H. pylori binding to the epithelium (11)(12)(13)(14)(15)(16)(17), it is not clear which cell and bacterial factors stimulate host cell apoptosis.…”

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confidence: 99%

Helicobacter pylori Urease Binds to Class II MHC on Gastric Epithelial Cells and Induces Their Apoptosis

Fan

Gunasena

Cheng

et al. 2000

The Journal of Immunology

147

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Infection by Helicobacter pylori leads to injury of the gastric epithelium and a cellular infiltrate that includes CD4+ T cells. H. pylori binds to class II MHC molecules on gastric epithelial cells and induces their apoptosis. Because urease is an abundant protein expressed by H. pylori, we examined whether it had the ability to bind class II MHC and induce apoptosis in class II MHC-bearing cells. Flow cytometry revealed the binding of PE-conjugated urease to class II MHC+ gastric epithelial cell lines. The binding of urease to human gastric epithelial cells was reduced by anti-class II MHC Abs and by staphylococcal enterotoxin B. The binding of urease to class II MHC was confirmed when urease bound to HLA-DR1-transfected COS-1 (1D12) cells but not to untransfected COS-1 cells. Urease also bound to a panel of B cell lines expressing various class II MHC alleles. Recombinant urease induced apoptosis in gastric epithelial cells that express class II MHC molecules, but not in class II MHC− cells. Also, Fab from anti-class II MHC and not from isotype control Abs blocked the induction of apoptosis by urease in a concentration-dependent manner. The adhesin properties of urease might point to a novel and important role of H. pylori urease in the pathogenesis of H. pylori infection.

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“…Recently, the carbohydrate structure sulfo-Le a was identified as an adhesion molecule for H. pylori (42,43). In saliva, sulfo-Le a is uniquely present on the glycoprotein MUC5B 1 , terminating the carbohydrate chains linked to this glycoprotein (10).…”

Section: Introductionmentioning

confidence: 99%

Salivary MUC5B-Mediated Adherence (Ex Vivo) of Helicobacter pylori During Acute Stress

Bosch

Geus

Ligtenberg

et al. 2000

Psychosomatic Medicine

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Objective: Biochemical host defenses at mucosal sites, such as the oral cavity, play a key role in the regulation of microbial ecology and the prevention of infectious disease. These biochemical factors have distinct features, some of which benefit the host and some that benefit bacteria. We investigated the effects of acute stress on the salivary levels of the carbohydrate structure sulfo-Lewis a (sulfo-Le a ), which is linked to the mucosal glycoprotein MUC5B. Sulfo-Le a was recently identified as an adhesion molecule for Helicobacter pylori; therefore, we also measured saliva-mediated adherence (ex vivo) of H. pylori. The oral cavity is suspected to be involved in the transmission of H. pylori. Methods: Saliva was collected from 17 undergraduates before (baseline), during (stress), and after (recovery) exposure to a video showing surgical procedures. In addition, blood pressure, an impedance cardiogram, and an electrocardiogram were recorded. Results: During stressor exposure, participants reported increased state anxiety. In addition, stroke volume increased and heart rate decreased. The stressor induced a strong increase in salivary sulfo-Le a concentration (U/ml), sulfo-Le a output (U/min), sulfo-Le a /total protein ratio (U/mg protein), and saliva-mediated adherence (ex vivo) of H. pylori. As expected, sulfo-Le a concentration correlated with the adherence of H. pylori (r ϭ 0.72, p Ͻ .05). It was demonstrated that the observed adherence was induced by MUC5B and that the carbohydrate structure sulfo-Le a contributed to this process. Conclusions: Our study demonstrated a direct link between stress-mediated biochemical changes and altered host-microbe interactions in humans. Increased bacterial adherence may be a contributing factor in the observed relationship between stress and susceptibility to infectious disease.

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Sulfated glycans on oral mucin as receptors for Helicobacter pylori

Cited by 80 publications

References 30 publications

Thickened saliva after effective management of drooling with botulinum toxin A

Thickened saliva after effective management of drooling with botulinum toxin A

Helicobacter pylori Urease Binds to Class II MHC on Gastric Epithelial Cells and Induces Their Apoptosis

Salivary MUC5B-Mediated Adherence (Ex Vivo) of Helicobacter pylori During Acute Stress

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