Role of platelet-activating factor in pancreatitis-associated acute lung injury in the rat.
Acute necrotizing pancreatitis induced by infusion of bile salt into the pancreatic duct in rats is consistently associated with acute lung injury similar to the adult respiratory distress syndrome. The role of platelet-activating factor (PAF) in this pancreatitis-associated remote organ failure (lung injury) was investigated. Pulmonary tissue levels of PAF were increased gradually and reached a level of 1345 +/- 455 pg/g (6 times the control level) at 12 hours after induction of pancreatitis, whereas pancreatic PAF levels were undetectable and blood PAF remained unchanged. This local pulmonary PAF accumulation occurred at approximately the same time as the progression of lung injury. Pulmonary responses detected (i.e., eicosanoid production, leukocytic infiltration, Evan's blue extravasation, beta-glucuronidase release) were attenuated to varying degrees by treatment of rats in which pancreatitis was initiated with the PAF receptor antagonists (WEB2170 and BN52021). Rat lung lavages were examined after a 12-hour course of pancreatitis and no changes in PAF concentration, surfactant content, and phospholipase A2 (PLA2) activity were noted. Intravenous administration of PLA2 promoted pulmonary PAF production in experimental rats with pancreatitis but not in normal rats. This observation indicates that PLA2, which was determined to be elevated in plasma during pancreatitis, may be responsible for the accumulation of PAF in the lung. In conclusion, pancreatitis-associated lung injury appears to result from an endogenous inflammatory response in which PAF may play an important role.
Zhou
W
W
Audie L. Murphy Veterans Memorial Hospital, University of Texas Health Science Center, San Antonio 78284-7760.
McCollum
M O
MO
Levine
B A
BA
Olson
M S
MS
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D004224:Diterpenes; D015777:Eicosanoids / Q000378:metabolism; D004798:Enzymes / Q000097:blood; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D010195:Pancreatitis / Q000473:pathology*; D010972:Platelet Activating Factor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D004224:Diterpenes; D015777:Eicosanoids; D004798:Enzymes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; C063964:bepafant; C045856:ginkgolide B