CD11B BLOCKADE PREVENTS LUNG INJURY DESPITE NEUTROPHIL PRIMING ALTER GUT ISCHEMIA-REPERFUSION

Gut ischemia/reperfusion (I/R) provokes lung injury via a mechanism that involves neutrophils [polymorphonuclear neutrophils (PMNs)]. CD11b/CD18 (alpha mB(2)) is the integrin receptor on PMNs critical for adhesion-dependent oxidative burst, The purpose of this study was to investigate the mechanistic role of CD11b in the process of gut I/R-induced lung injury. Sprague-Dawley rats underwent 45 minutes of superior mesenteric artery (SMA) occlusion with and without CD11b monoclonal antibody treatment (IB6) (1 mg/kg, IV), before SMA clamping. At 2-hour reperfusion, PMN presence in tissue was quantitated by myeloperoxidase activity and circulating PMN priming determined by the difference in superoxide production with and without N-formyl-methionyl-leucyl-phenylalanine, whereas lung leak was assessed by I-125-albumin lung/blood ratio. In sum, CD11b blockade prevented gut UR-induced lung leak, but did not attenuate gut I/R-induced PMN priming or tissue PMN accumulation, In conclusion, gut I/R promotes PMN priming and PMN adhesion in both local and distant beds via receptors other than CD11b, but this B-2 integrin receptor is critical for PMN-mediated endothelial injury.