Phospholipase A2 inhibition decouples lung injury from gut ischemia-reperfusion.
BACKGROUND
Phospholipase A2 (PLA2) has recently been implicated as a key enzyme of local inflammation after gut ischemia-reperfusion (I/R). The hypothesis of this study is that PLA2 inhibition decouples remote organ injury from gut I/R.


METHODS
Sprague-Dawley rats were pretreated with a PLA2 inhibitor, quinacrine (10 mg/kg, intravenously), before the induction of gut ischemia (45 minutes of superior mesenteric artery occlusion) followed by 6 hours of reperfusion. 125I-labeled albumin leak was employed as a marker of pulmonary endothelial permeability and myeloperoxidase as a monitor of neutrophil (PMN) traffic in the gut and lung. To further characterize the impact of PLA2 inhibition, PMNs were harvested at 6 hours of reperfusion and superoxide production was measured in the presence or absence of an activating stimulus, N-formyl-methionyl-leucyl-phenylalanine.


RESULTS
Gut I/R increased gut PLA2 activity, elicited gut PMN influx, and produced lung leak; these events were prevented by PLA2 blockade. Gut I/R also markedly enhanced PMN superoxide production with N-formyl-methionyl-leucyl-phenylalanine, and this priming was ablated by PLA2 inhibition.


CONCLUSIONS
These data suggest that PLA2 activation is a proximal step in the pathogenesis of distant organ injury after splanchnic hypoperfusion, a process that appears to involve PMN priming in the gut bed.
Koike
K
K
Department of Surgery, Denver General Hospital, Colo.
Moore
E E
EE
Moore
F A
FA
Carl
V S
VS
Pitman
J M
JM
Banerjee
A
A
D000818:Animals; D002199:Capillary Permeability; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000473:pathology*; D012709:Serum Albumin / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D012709:Serum Albumin; D013481:Superoxides; D009195:Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2