Group IIA phospholipase A2 mediates lung injury in intestinal ischemia-reperfusion

Objective To assess the mechanistic role of group IIA phospholipase A(2) (PLA(2)) in the process of local and distant organ injury after intestinal ischemia-reperfusion. Summary Background Data Intestinal ischemia-reperfusion produces lung injury by a mechanism that involves PLA(2) activation, but it is unclear which isozyme is responsible for this phenomenon. Group IIA PLA(2), one of the secreted forms of PLA(2), is known to play a pivotal role in a variety of inflammatory reactions. Methods Rats underwent 45 minutes of superior mesenteric artery occlusion in the presence and absence of pretreatment with group IIA PLA(2) inhibitor, S-5920/LY315920Na (20 mg/kg, subcutaneously, 30 minutes before clamping). At 2 hours of reperfusion, intestinal and lung leak was assessed by I-125-albumin tissue/blood ratio, and liver injury was estimated by serum alanine aminotransferase. PLA(2) activities in tissues and sera were quantitated by phosphatidyl-glycerol/sodium cholate mixed micelle assay, PLA(2) activities in tissues were also measured after in vitro preincubation with EDTA, S-5920/LY315920Na, or antirat group IIA PLA(2) antibody. Results Intestinal ischemia-reperfusion provoked intestinal leak, liver injury, and lung leak, whereas tissue PLA(2) activity was decreased in the intestine, unchanged in the liver, and increased in the lung. Serum PLA(2) activities were increased in the portal and systemic circulation during ischemia, Pretreatment with S-5920/LY315920Na eliminated PLA(2) activities in all tissues and sera and only abolished lung leak. The in vitro experiment revealed that most of the intestinal and lung PLA(2) activities were inhibited by EDTA, S-5920/LY315920Na, and antirat group IIA PLA(2) antibody, but hepatic PLA(2) activity was not. Conclusion Intestinal ischemia-reperfusion appears to produce lung injury by a mechanism that involves group IIA PLA(2) activation. Intestinal ischemia-reperfusion is likely to promote intestinal and hepatic injury independent of group IIA PLA(2).