PAF, a proinflammatory phospholipid mediator, is degraded by PAF specific AH. The regulation of AH was studied in a rat model of PAF-induced intestinal injury. We found that PAF-AH activity increased in both plasma and intestine 1.5 h after PAF (1.5 μg/kg, iv) administration. Cyclohexamide (CHX, 5 mg/kg, iv) reduced AH activity in the plasma (but not in the intestine) in control as well as in PAF-injected rats, and aggravated systemic inflammation and tissue injury in the latter. The intestinal necrosis induced by PAF and CHX (30 min before PAF) was ameliorated by pretreament with anti-TNF mAb or post-treatment (20 min after PAF) with WEB2170 indicating a role of endogenous PAF and TNF in mediating injury. Both WEB2170 and anti-TNF antibody reduced PAF-induced AH activity in intestinal tissue, but not in the plasma. Allopurinol largely prevented the injury induced by PAF and CHX, but had no effect on the upregulation of AH. We conclude: (1) PAF upregulates plasma AH which depends on new protein synthesis. (2) Endogenous PAF and TNF play a role in the upregulation of intestinal AH and in the intestinal injury induced by combined treatment of CHX and PAF. (3) Reactive oxygen species mediates the injurious effect of PAF and CHX, but does not contribute to the regulation of AH by PAF.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology