Platelet-activating Factor Mediates Endotoxin-induced Lung Injury in Dogs and Its Mechanism / 第二军医大学学报

ABSTRACT

Intravenous administration of E. coli endotoxin (2mg/kg) caused a persistent increase in platelet activating factor (PAF) contents in arterial blood and bronchoalveolar fluid (BALF). Meanwhile phospholipase A2(PLA2) activity in serum and BALF was elevated and mean arterial blood pressure declined. The total cell number, expecially polymorphonuclear leukocytes and lymphocytes, and protein concentration in BALF were markedly increased 6 h after endotoxin injection. Lung index and extravascular lung water content of endotoxin-treated animals were significantly highter than those of controls. Pretreatment with PAF receptor antagonist SRI 63-441 blocked the increase in PLA, activity and attenuated endotoxin-induced hypotension and acute lung injury. The results suggest that PAF mediates endotoxin-induced lung injury, and leukocyte activation by PAF and the subsequent release of oxygen metabolites and lysoenzymes are important intermediate mechanisms leading to high permeability pulmonary edema.