Galectin-3 binds to Helicobacter pylori O-antigen: it is upregulated and rapidly secreted by gastric epithelial cells in response to H. pylori adhesion.
Helicobacter pylori causes gastritis and some infections result in peptic ulceration, gastric adenocarcinoma or gastric lymphoma. A critical step in the pathogenesis of these diseases is the ability of H. pylori to adhere to gastric epithelial cells. A role for the lipopolysaccharide O-antigen side-chain in this process has previously been identified. In this study, evidence is presented that the receptor recognized by the O-antigen side-chain is galectin-3, a beta-galactoside-binding lectin. A variety of functions have been ascribed to galectin-3 including modulation of extracellular adhesion and chemotaxis of monocytes and neutrophils. Expression of galectin-3 is upregulated by gastric epithelial cells following adhesion of H. pylori, suggesting that in addition to colonization this protein also plays a role in the host response to infection. Upregulation of galectin-3 is inhibited by treating gastric epithelial cells with the mitogen-activated protein kinase (MAPK) inhibitors U0126 or PD098059 and does not occur in cells infected with either H. pylori cagE or cagA isogenic mutants. This implies that H. pylori-mediated expression of galectin-3 is dependent on delivery of CagA into the host cell cytosol and the subsequent stimulation of MAPK signalling. A further consequence of H. pylori adhesion is that it elicits a rapid release of galectin-3 from infected cells. A role for this phenomenon in initiating the trafficking of phagocytic cells to the site of infection is discussed.
Fowler
Mark
M
University of Manchester, Faculty of Life Science, 1.800 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Thomas
Rachael J
RJ
Atherton
John
J
Roberts
Ian S
IS
High
Nicola J
NJ
D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000502:physiology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D037502:Galectin 3 / Q000096:biosynthesis / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019081:O Antigens / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D037502:Galectin 3; D019081:O Antigens; D012333:RNA, Messenger; C080866:cagA protein, Helicobacter pylori