Scientists have determined that decay-accelerating factor (DAF), a protein found in epithelial cells in the stomach, acts as a receptor for the bacteria Helicobacter pylori. Blocking this interaction could lead to new drugs that reduce the risk of peptic ulcer disease or gastric cancer. The research appears as the "Paper of the Week" in the May 12 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.
Helicobacter pylori are spiral shaped bacteria that live in the thick layer of mucus that covers the stomach lining. The bacteria are found everywhere in the world, but are especially prevalent in developing countries, where up to 80% of children and 90% of adults can have laboratory evidence of an H. pylori infection--usually without having any symptoms.
The vast majority of H. pylori in colonized hosts are free-living, but approximately 20% bind to gastric epithelial cells. This binding induces an immune response and alters the morphology and behavior of the epithelial cells due to injection of bacterial proteins into the cells. This interaction can lead to peptic ulcer disease, gastric adenocarcinoma, and non-Hodgkins lymphoma of the stomach.
"Ulcers are a breach in the gastric or duodenal mucosa and gastric adenocarcinoma is one type of cancer of the stomach," explains senior author Dr. Richard M. Peek, Jr. of the Vanderbilt University School of Medicine. "H. pylori alters acid production and can lead to increased acid outputs which causes peptic ulcer disease. The means through which H. pylori causes gastric cancer are more complex but likely involve alterations in gastric epithelial cell responses that are perturbed within the context of a chronic gastric inflammatory infiltrate, which can persist for decades."
A membrane-imbedded protein found in the stomach called decay-accelerating factor (DAF) has been shown to function as a receptor for several microbial pathogens. Peek and his colleagues were curious as to whether DAF was also involved in H. pylori adherence. To do this, the researchers measured the number of H. pylori that bound to cells that either expressed or did not express DAF. They found that the bacteria do indeed adhere to cells with DAF. They also discovered that H. pylori induce DAF expression in cultured gastric epithelial cells and that mice lacking DAF develop attenuated stomach inflammation.
"Our results indicate that H. pylori can co-opt a host protein as a receptor and that it can increase expression of this receptor in gastric epithelial cells," says Peek. "Further, absence of this receptor abolishes the inflammatory response that H. pylori induces in infected mice, suggesting that this receptor mediates H. pylori-induced injury in the stomach."
These findings suggest that drugs that interfere with DAF binding could be used to prevent or treat peptic ulcer disease or distal gastric adenocarcinoma. These new drugs will be a welcome alternative to the current treatment for H. pylori infections which typically involves taking 3 to 4 medications over a 10 to 14 day period.
The Journal of Biological Chemistry's Papers of the Week is an online feature which highlights the top one percent of papers received by the journal. Brief summaries of the papers and explanations of why they were selected for this honor can be accessed directly from the home page of the Journal of Biological Chemistry online at www.jbc.org.
The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization with over 11,000 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions, and industry.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's primary purpose is to advance the sciences of biochemistry and molecular biology through its publications, the Journal of Biological Chemistry, the Journal of Lipid Research, Molecular and Cellular Proteomics, and Biochemistry and Molecular Biology Education, and the holding of scientific meetings.
For more information about ASBMB, see the Society's website at www.asbmb.org
(C) 2006 - The American Society for Biochemistry and Molecular Biology
O'brien DP, Israel DA, Krishna U, Romero-Gallo J, Nedrud J, Medof ME, Lin F, Redline R, Lublin DM, Nowicki BJ, Franco AT, Ogden S, Williams AD, Polk DB, Peek RM Jr.
The Role of Decay-accelerating Factor as a Receptor for Helicobacter pylori and a Mediator of Gastric Inflammation.
J Biol Chem. 2006 May 12;281(19):13317-23.
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