Induction of nitric oxide synthesis in murine macrophages by Helicobacter pylori.

Intact Helicobacter pylori cells, as well as cellular components, stimulated nitric oxide (NO) synthesis in an in vitro murine macrophage system by the L-arginine-nitric oxide pathway. Macrophage-mediated NO formation was dependent on the presence of H. pylori and exhibited a dose-dependent increase at H. pylori concentrations between 10(6) and 5 and 10(7) cells/ml. H. pylori mediated NO synthesis also required L-arginine and was inhibited by NG-monomethyl-L-arginine (NMMA), a selective inhibitor of nitric oxide synthase. NO synthesis was induced by whole H. pylori cells. H. pylori media filtrate, extracted membrane proteins, and H. pylori lipopolysaccharide (LPS). Maximal NO synthesis was induced by viable H. pylori cells with media filtrate and membrane protein extracts inducing significant NO responses. NO stimulation by media filtrate and membrane protein extracts support secreted H. pylori products as potential activators of inflammatory cell NO synthesis in vivo. NO synthesis in response to H. pylori suggests that chronic H. pylori infection may increase endogenous formation of NO. Elevated NO exposure may represent an etiologic factor explaining the epidemiologic association between long-term H. pylori infection and gastric cancer.