The role of decay-accelerating factor as a receptor for Helicobacter pylori and a mediator of gastric inflammation.

Abstract	Persistent gastritis induced by Helicobacter pylori is the strongest known risk factor for peptic ulcer disease and distal gastric adenocarcinoma, a process for which adherence of H. pylori to gastric epithelial cells is critical. Decay-accelerating factor (DAF), a protein that protects epithelial cells from complement-mediated lysis, also functions as a receptor for several microbial pathogens. In this study, we investigated whether H. pylori utilizes DAF as a receptor and the role of DAF within H. pylori-infected gastric mucosa. In vitro studies showed that H. pylori adhered avidly to Chinese hamster ovary cells expressing human DAF but not to vector controls. In H. pylori, disruption of the virulence factors vacA, cagA, and cagE did not alter adherence, but deletion of DAF complement control protein (CCP) domains 1-4 or the heavily O-glycosylated serine-threonine-rich COOH-terminal domain reduced binding. In cultured gastric epithelial cells, H. pylori induced transcriptional up-regulation of DAF, and genetic deficiency of DAF attenuated the development of inflammation among H. pylori-infected mice. These results indicate that DAF may regulate H. pylori-epithelial cell interactions relevant to pathogenesis.
Authors	Daniel P O'Brien, Dawn A Israel, Uma Krishna, Judith Romero-Gallo, John Nedrud, M Edward Medof, Feng Lin, Raymond Redline, Douglas M Lublin, Bogdan J Nowicki, Aime T Franco, Seth Ogden, Amanda D Williams, D Brent Polk, Richard M Peek Jr
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 19 Pg. 13317-13323 (May 12 2006) ISSN: 0021-9258 [Print] United States
PMID	16543227 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	CD55 Antigens
Topics	Animals Bacterial Adhesion CD55 Antigens (genetics, metabolism) CHO Cells Cricetinae Gene Deletion Gene Expression Regulation Helicobacter pylori (metabolism) Humans Inflammation (metabolism, microbiology) Mice Mice, Knockout Stomach Diseases (metabolism, microbiology)

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