Inhibition of apoptosis in human neutrophils by Helicobacter pylori water-soluble surface proteins

Background: Helicobacter pylori infection in humans causes persistent neutr ophil infiltration into the gastric mucosa. It is believed that a prolongat ion of neutrophil life-span could contribute to the pathogenesis of H. pylo ri infection. We therefore examined whether the water-soluble surface prote ins of H. pylori can influence the apoptosis of neutrophils. Methods: After neutrophils were incubated with H. pylori water extract (HPWE), neutrophil apoptosis was evaluated by TUNEL, assay, Hoechst 33342 staining, electron microscopy and ELISA for cytosolic oligonucleosome-bound DNA for up to 48 h . To investigate the regulatory mechanisms of neutrophil apoptosis associat ed with HPWE, mRNA expression and protein production of Fas, Fas ligand (Fa sL) and tumor necrosis factor receptor 1 (TNF-R1) were analyzed by RT-PCR, ribonuclease protection assay, Northern blot and Western blotting. Cell sur face expression of these death factors was also measured by flow cytometry. Results: HPWE inhibited neutrophil apoptosis and cytotoxicity for up to 48 h. The mRNA and protein expression of Fast and the cell surface expression of Fas, Fast and TNF-R1 in HPWE-treated neutrophils were suppressed compar ed with the controls. Conclusion: The water-soluble surface proteins of H. pylori could suppress neutrophil apoptosis. This may be caused by the suppr ession of Fast expression in neutrophils and Fas, Fast and TNF-R1 expressio n on the surface of neutrophils.