Inhibition of apoptosis in human neutrophils by Helicobacter pylori water-soluble surface proteins.
BACKGROUND
Helicobacter pylori infection in humans causes persistent neutrophil infiltration into the gastric mucosa. It is believed that a prolongation of neutrophil life-span could contribute to the pathogenesis of H. pylori infection. We therefore examined whether the water-soluble surface proteins 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 associated with HPWE, mRNA expression and protein production of Fas, Fas ligand (FasL) and tumor necrosis factor receptor 1 (TNF-R1) were analyzed by RT-PCR, ribonuclease protection assay, Northern blot and Western blotting. Cell surface 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 FasL and the cell surface expression of Fas, FasL and TNF-R1 in HPWE-treated neutrophils were suppressed compared with the controls.


CONCLUSIONS
The water-soluble surface proteins of H. pylori could suppress neutrophil apoptosis. This may be caused by the suppression of FasL expression in neutrophils and Fas, FasL and TNF-R1 expression on the surface of neutrophils.
Kim
J S
JS
Dept. of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, 110-744 Seoul, Korea.
Kim
J M
JM
Jung
H C
HC
Song
I S
IS
Kim
C Y
CY
D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000378:metabolism*; D053222:Fas Ligand Protein; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047990:TNF Receptor-Associated Factor 1; D019014:fas Receptor / Q000378:metabolism
D001426:Bacterial Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; D019014:fas Receptor