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By Will Boggs, MD

WESTPORT, CT (Reuters Health) – Helicobacter pylori produce a peptide that activates monocytes to reduce the function and viability of antineoplastic lymphocytes, according to a report in the October 15th Journal of Clinical Investigation.

H. pylori infection has been linked epidemiologically with the development of gastric adenocarcinoma, the authors note, but the mechanism behind the increased cancer risk has not been clarified.

Because chronic inflammation accompanies H. pylori infection, Dr. Kristoffer Hellstrand from the University of Goteborg, Sweden, and colleagues explored the immunomodulatory properties of Hp(2-20), a cecropin-like peptide derived from H. pylori.

Hp(2-20) dose-dependently attracted and activated human monocytes in vitro, the authors report, inducing a robust production of oxygen radicals that was inhibited by NADPH-oxidase inhibitor.

Hp(2-20) also effectively enhanced the suppression of natural killer cells by monocytes, the researchers note, and it induced the disappearance of a critical signal-transducing molecule from natural killer cell-enriched lymphocytes. This suppression was blocked by superoxide dismutase and catalase.

Lymphocytes incubated overnight in the presence of Hp(2-20)-activated monocytes showed apoptotic changes similar to those found in lymphocytes recovered from patients with advanced gastric carcinoma, the results indicated.

"Hp(2-20) peptide may contribute to the recruitment and activation of monocyte/macrophages to the inflammatory tissue of H. pylori-infected gastric tissue," the authors hypothesize. "Our data may also have implications for the carcinogenesis in chronically infected gastritis tissue."

In H. pylori-related carcinogenesis, "the oxygen radicals produced in response to the bacterial peptide are toxic to DNA with ensuing risk for malignant transformation," Dr. Hellstrand told Reuters Health. "In addition, the radicals shut down lymphocytes known to participate in the surveillance of malignant cells–a double-edged sword."

"Histamine, which is present at high concentrations in normal gastric tissue, inhibits the H. pylori-induced oxygen radical formation and protects anti-neoplastic lymphocytes against H. pylori-induced functional inhibition and apoptosis," Dr. Hellstrand said. "Possibly, endogenous histamine protects immune effector lymphocytes against oxygen radical damage in inflammatory tissue, including malignant tumors."

Dr. Hellstrand suggested that "anti-oxidative compounds–including scavengers of oxygen radicals or inhibitors of radical formation–could be useful in enhancing the function of lymphocytes in gastric tissue."