He role of leukocyte adhesion in paf-induced type ii phospholipase a₂ (pla₂-ii) activation in the small intestine

PLA2-II is an enzyme important in inflammatory processes, which is preferentially localized in the intestinal crypts. We have previously shown that PAF activates intestinal PLA2-II. In this study we examined the role of anti-CDllb, anti-P-selectin, and anti-TNF in PAF-induced PLAj-II activation. Adult S.D. rats were injected with PAF at a dose beneath that causing shock and gross bowel injury (1.5 fig/kg, iv), and the small bowel was removed for assays of PLA2-II and MPO at 30 min. Some rats were pretreated with anti-rat CD1 Ib MAb (1B6, 1.5 mg/kg, iv), anti-P-selectin MAb (PB1.3, 2 mg/kg, iv) or anti-TNF serum (2.5 ml/kg, ip) 30 min before PAF. We found that anti-P-selectin and antiTNF significantly blocked the PAF-induced PLA2-II activation. The inhibitory effect by anti-CDllb was marginally significant. PAF caused an increase in intestinal MPO activity which was reduced by pretreatment with anti-CDlIb, anti-P-selectin and anti-TNF. We conclude that PAFinduced activation of PLA2-II in the small intestine results from leukocyte-endothelial interactions mediated by adhesion molecules such as P-selectin and probablv CDllb. TNF also appears to be involved in PAF-induced PLA2-II activation.