Platelet activating factor (PAF) induces intestinal epithelial apoptosis: Role of polymorphonuclear leukocytes

We have previously demonstrated that systemic administration of PAF (2.5 to 3 μg/kg, i.v,) into rats or mice causes shock and intestinal necrosis. Injection of 1.5 μg/kg PAF or a lower dose usually results in only transient hypotension and leukocytosis, without developing gross bowel injury. In the present study, we examined whether low doses of PAF induce intestinal apoptosis. Adult S.D. rats were injected with PAF (1.5 μg/kg, i.v.) and were sacrificed 30 minutes later. Visceral organs including small intestine, colon, stomach, lung, liver, and kidneys were processed for TUNEL stain to examine cell apoptosis. We found that the small intestine in normal rats shows rare epithelial apoptosis. 30 min after PAF, there was a significant increase in the number of apoptotic cells in small intestinal epithelia, mostly in the upper half of the villi. The lamina propria cells rarely showed apoptosis. Apoptosis could not be detected in other organs. We then examined whether PAF-induced intestinal epithelial apoptosis is mediated via PMN activation. We found that PMN depleted rats (by anti-PMN antibody treatment) were protected from PAF-induced intestinal epithelial apoptosis. Thus, PAF induces intestinal epithelial apoptosis which is probably mediated by PMN activation.