Gut phospholipase A2 mediates neutrophil priming and lung injury after mesenteric ischemia-reperfusion.
Intestinal ischemia-reperfusion (I/R) provokes polymorphonuclear neutrophil (PMN)-mediated lung injury via a process characterized by circulating PMN priming, pulmonary PMN sequestration, and increased microvascular leak in the lung. We found in rats subjected to intestinal I/R (ischemia 45 min and reperfusion 6 h) that 1) intestinal phospholipase A2 (PLA2) was activated during ischemia, 2) circulating PMN priming (assessed by superoxide production with N-formyl-Met-Leu-Phe) occurred after 1 h reperfusion, and 3) exaggerated 125I-labeled albumin lung leak occurred after 2 h reperfusion, compared with sham-treated animals (P < 0.05). Treatment with a PLA2 inhibitor, quinacrine, within 15 min of reperfusion reversed the exaggerated gut PLA2 activity and abrogated subsequent PMN priming and lung leak (P < 0.05). However, when quinacrine was administered after 2 h of reperfusion, circulating PMN priming and lung leak continued to evolve despite suppression of intestinal PLA2 activity. We conclude that intestinal PLA2 activation may be a prerequisite for the sequelae of circulating PMN priming and pulmonary microvascular leak observed after intestinal I/R.
Koike
K
K
Department of Surgery, Denver General Hospital, Colorado.
Moore
E E
EE
Moore
F A
FA
Kim
F J
FJ
Carl
V S
VS
Banerjee
A
A
D000818:Animals; D004789:Enzyme Activation; D007422:Intestines / Q000098:blood supply / Q000201:enzymology*; D007511:Ischemia; D007700:Kinetics; D008171:Lung Diseases / Q000209:etiology*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D012711:Serum Albumin, Radio-Iodinated / Q000378:metabolism; D013152:Splanchnic Circulation; D013481:Superoxides / Q000097:blood
D012711:Serum Albumin, Radio-Iodinated; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine