Role of apoptosis in gastric epithelial turnover

Gastric epithelial turnover is a dynamic process. It is characterized by co ntinous cell proliferation, which is counterbalanced by cell loss. The biol ogical principle that mediates the homeostasis of epithelium is programmed cell death, or apoptosis. Currently, several subtypes of apoptosis are dist inguished, which are mediated by different mechanisms. Various subtypes of apoptosis also occur in the gastric epithelium under various conditions. In the normal stomach, apoptosis due to cell isolation (anoikis) mediates the physiological epithelial turnover. Albeit rarely seen in routine histology , approximately 2% of epithelial cells in the normal stomach are apoptotic. In Helicobacter pylori-induced gastritis, apoptosis and epithelial prolife ration are moderately increased, with approximately 8% apoptotic epithelial cells. In gastritis, factors such as CD95 ligand or tumor necrosis factor (TNF) alpha act as death factors. They bind to specific receptors, CD95 and TNF-R, which are induced either by other cytokines, such as interferon gam ma, or by Helicobacter pylori itself In addition to CD95, H. pylori can als o induce upregulation of CD95 ligand expression. Taken together, the upregu lated expression of CD95, and the presence of CD95L in the close proximity to apoptotic gastric epithelial cells suggest a functional role of the CD95 -CD95L system in the induction of apoptosis in H. pylori-gastritis. The rol e of other pathways to apoptosis is currently under study. Apart from being a biological phenomenon, apoptosis in the stomach may also have direct cli nical consequences. An extreme example is given in gastric graft-vs.-host d isease when epithelial denudement occurs. (C) 2000 Wiley-Liss, Inc.