The role of decay-accelerating factor as a receptor for Helicobacter pylori and a mediator of gastric inflammation.
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.
Division of Gastroenterology, Departments of Medicine, Pediatrics, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279.
Daniel P
DP
O'Brien
Division of Gastroenterology, Departments of Medicine, Pediatrics, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279.
Dawn A
DA
Israel
Division of Gastroenterology, Departments of Medicine, Pediatrics, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279.
Uma
U
Krishna
Division of Gastroenterology, Departments of Medicine, Pediatrics, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279.
Judith
J
Romero-Gallo
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
John
J
Nedrud
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
M Edward
ME
Medof
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Feng
F
Lin
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Raymond
R
Redline
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Douglas M
DM
Lublin
Departments of Obstetrics & Gynecology and Biomedical Sciences and Division of Microbial Pathogenesis and Immune Response, Meharry Medical Center, Nashville, Tennessee 37208.
Bogdan J
BJ
Nowicki
Division of Gastroenterology, Departments of Medicine, Pediatrics, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279.
Aime T
AT
Franco
Division of Gastroenterology, Departments of Medicine, Pediatrics, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279.
Seth
S
Ogden
Division of Gastroenterology, Departments of Medicine, Pediatrics, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279.
Amanda D
AD
Williams
Division of Gastroenterology, Departments of Medicine, Pediatrics, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279.
D Brent
DB
Polk
Division of Gastroenterology, Departments of Medicine, Pediatrics, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279; Department of Veterans Affairs Medical Center, Nashville, Tennessee 37212. Electronic address: richard.peek@vanderbilt.edu.
Richard M
RM
Peek
D000818:Animals; D001422:Bacterial Adhesion; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D017353:Gene Deletion; D005786:Gene Expression Regulation; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D013272:Stomach Diseases / Q000378:metabolism / Q000382:microbiology*
D018958:CD55 Antigens