Effect of ammonium ion on the hydrophobic and barrier properties of the gastric mucus gel layer: Implications on the role of ammonium in H. pylori-induced gastritis

Current studies indicate that the anti-H. pylori protective efficacy of oral vaccines to a large extent depends on using mucosal adjuvants like E. coli heat-lable enterotoxin B unit (LtB). However, the mechanism by which Th17/Th1-driven cellular immunity kills H. pylori and the role of LtB remains unclear. Here, two L. lactis strains, expressing H. pylori NapA and LtB, respectively, were orally administrated to mice. As observed, the administration of LtB significantly enhanced the fecal SIgA level and decreased gastric H. pylori colonization, but also markedly aggravated gastric inflammatory injury. Both NapA group and NapA+LtB group had elevated splenocyte production of IL-8, IL-10, IL-12, IL-17, IL-23 and INF-γ. Notably, gastric leukocytes’ migration or leakage into the mucus was observed more frequently in NapA+LtB group than in NapA group. This report is the first that discusses how LtB enhances vaccine-induced anti-H. pylori efficacy by aggravating gastric injury and leukocytes’ movement into the mucus layer. Significantly, it brings up a novel explanation for the mechanism underlying mucosal cellular immunity destroying the non-invasive pathogens. More importantly, the findings suggest the necessity to further evaluate LtB’s potential hazards to humans before extending its applications. Thus, this report can provide considerable impact on the fields of mucosal immunology and vaccinology.

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Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised

Gut ◽

10.1136/gut.43.4.470 ◽

1998 ◽

Vol 43 (4) ◽

pp. 470-475 ◽

Cited By ~ 26

Author(s):

J L Newton ◽

N Jordan ◽

L Oliver ◽

V Strugala ◽

J Pearson ◽

...

Keyword(s):

Helicobacter Pylori ◽

Structural Changes ◽

Endoscopic Biopsy ◽

Gastric Atrophy ◽

Mucus Layer ◽

Gastric Mucus ◽

Mucus Gel ◽

Mucus Barrier ◽

H Pylori

Background—It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial.Aims—To clarify the effects of H pylori infection on the mucus gel barrier in vivo.Methods—Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pyloriinfection.Results—There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness betweenH pylori positive and negative subjects without gastric atrophy (mean (SD): 104 (26) μm, 106 (30) μm respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) μm, p=0.03) compared with those without atrophy.Conclusions—A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insufficient to cause a collapse of the mucus barrier.

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Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin

AJP Cell Physiology ◽

10.1152/ajpcell.00102.2004 ◽

2005 ◽

Vol 288 (1) ◽

pp. C1-C19 ◽

Cited By ~ 371

Author(s):

Adrian Allen ◽

Gunnar Flemström

Keyword(s):

Ph Gradient ◽

Support Surface ◽

First Line ◽

Physiological Conditions ◽

Neutral Ph ◽

Primary Function ◽

Gel Layer ◽

Mucus Gel ◽

And Control

Secretion of bicarbonate into the adherent layer of mucus gel creates a pH gradient with a near-neutral pH at the epithelial surfaces in stomach and duodenum, providing the first line of mucosal protection against luminal acid. The continuous adherent mucus layer is also a barrier to luminal pepsin, thereby protecting the underlying mucosa from proteolytic digestion. In this article we review the present state of the gastroduodenal mucus bicarbonate barrier two decades after the first supporting experimental evidence appeared. The primary function of the adherent mucus gel layer is a structural one to create a stable, unstirred layer to support surface neutralization of acid and act as a protective physical barrier against luminal pepsin. Therefore, the emphasis on mucus in this review is on the form and role of the adherent mucus gel layer. The primary function of the mucosal bicarbonate secretion is to neutralize acid diffusing into the mucus gel layer and to be quantitatively sufficient to maintain a near-neutral pH at the mucus-mucosal surface interface. The emphasis on mucosal bicarbonate in this review is on the mechanisms and control of its secretion and the establishment of a surface pH gradient. Evidence suggests that under normal physiological conditions, the mucus bicarbonate barrier is sufficient for protection of the gastric mucosa against acid and pepsin and is even more so for the duodenum.

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Use of Fluorescent Hydrophobic Dyes in Establishing the Presence of Lipids in the Gastric Mucus Gel Layer

Journal of Clinical Gastroenterology ◽

10.1097/00004836-199206001-00014 ◽

1992 ◽

Vol 14 ◽

pp. S82-S87 ◽

Cited By ~ 6

Author(s):

Lenard M. Lichtenberger ◽

Tariq N. Ahmed ◽

José C. Barreto ◽

Ya-Chu Judy Kao ◽

Elizabeth J. Dial

Keyword(s):

Gastric Mucus ◽

Gel Layer ◽

Mucus Gel

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A new method of separation and quantitation of mucus glycoprotein in rat gastric mucus gel layer and its application to mucus secretion induced by 16,16-dimethyl PGE2

Gastroenterologia Japonica ◽

10.1007/bf02781673 ◽

1991 ◽

Vol 26 (5) ◽

pp. 582-587 ◽

Cited By ~ 9

Author(s):

Yuichi Komuro ◽

Kazuhiko Ishihara ◽

Susumu Ohara ◽

Katsunori Saigenji ◽

Kyoko Hotta

Keyword(s):

Mucus Secretion ◽

New Method ◽

Gastric Mucus ◽

Mucus Glycoprotein ◽

Gel Layer ◽

Mucus Gel

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Galectin-2 Has Bactericidal Effects against Helicobacter pylori in a β-galactoside-Dependent Manner

International Journal of Molecular Sciences ◽

10.3390/ijms21082697 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2697 ◽

Cited By ~ 1

Author(s):

Takaharu Sasaki ◽

Rei Saito ◽

Midori Oyama ◽

Tomoharu Takeuchi ◽

Toru Tanaka ◽

...

Keyword(s):

Helicobacter Pylori ◽

Bactericidal Effect ◽

Dependent Manner ◽

Peptic Ulcers ◽

Gastric Tissue ◽

Gastric Mucus ◽

Biological Phenomena ◽

Bactericidal Effects ◽

H Pylori

Helicobacter pylori is associated with the onset of gastritis, peptic ulcers, and gastric cancer. Galectins are a family of β-galactoside-binding proteins involved in diverse biological phenomena. Galectin-2 (Gal-2), a member of the galectin family, is predominantly expressed in the gastrointestinal tract. Although some galectin family proteins are involved in immunoreaction, the role of Gal-2 against H. pylori infection remains unclear. In this study, the effects of Gal-2 on H. pylori morphology and survival were examined. Gal-2 induced H. pylori aggregation depending on β-galactoside and demonstrated a bactericidal effect. Immunohistochemical staining of the gastric tissue indicated that Gal-2 existed in the gastric mucus, as well as mucosa. These results suggested that Gal-2 plays a role in innate immunity against H. pylori infection in gastric mucus.

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Interaction of Tea Polyphenols and Food Constituents with Model Gut Epithelia: The Protective Role of the Mucus Gel Layer

Journal of Agricultural and Food Chemistry ◽

10.1021/jf205111k ◽

2012 ◽

Vol 60 (12) ◽

pp. 3318-3328 ◽

Cited By ~ 17

Author(s):

Eleanor M. D’Agostino ◽

Damiano Rossetti ◽

Derek Atkins ◽

Dudley Ferdinando ◽

Gleb E. Yakubov

Keyword(s):

Protective Role ◽

Tea Polyphenols ◽

Gel Layer ◽

Mucus Gel

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Gastric Mucus Alterations Associated With Murine Helicobacter Infection

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.2009.952473 ◽

2009 ◽

Vol 57 (5) ◽

pp. 457-467 ◽

Cited By ~ 16

Author(s):

Julia M. Schmitz ◽

Carolyn G. Durham ◽

Samuel B. Ho ◽

Robin G. Lorenz

Keyword(s):

Adaptive Immune Response ◽

The Body ◽

Gastric Mucus ◽

Helicobacter Felis ◽

Adaptive Immune ◽

Mucous Metaplasia ◽

Mucin Expression ◽

Rag 1 ◽

H Pylori

The C57BL/6 mouse has been shown to develop gastric adenocarcinoma after Helicobacter felis infection. This model was used to determine whether mucin and trefoil factor (TFF) expression after infection was altered in a similar fashion to the changes seen in the protective gastric mucus layer of the human stomach after H. pylori infection. Our results indicate that this mouse model mimics many of the changes seen after human H. pylori infection, including increased expression of muc4 and muc5b and loss of muc5ac. These alterations in mucin expression occurred as early as 4 weeks postinfection, before the development of significant mucous metaplasia or gastric dysplasia. The decrease in muc5ac expression occurred only in the body of the stomach and was not secondary to the adaptive immune response to infection, because a similar decrease in expression was seen after infection of B6.Rag-1−/− mice, which lack B and T cells. Intriguingly, the increased expression of Muc4 and Muc5b in infected C57BL/6 mice was not seen in the infected B6.Rag-1−/− mice. Because B6.Rag-1−/− mice do not develop gastric pathology after H. felis infection, these findings point to the potential role of Muc4 and Muc5b in disease progression. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials. (J Histochem Cytochem 57:457–467, 2009)

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