CD11b blockade prevents lung injury despite neutrophil priming after gut ischemia/reperfusion.
Gut ischemia/reperfusion (I/R) provokes lung injury via a mechanism that involves neutrophils [polymorphonuclear neutrophils (PMNs)]. CD11b/CD18 (alpha mB2) 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, i.v.), 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 125I-albumin lung/blood ratio. In sum, CD11b blockade prevented gut I/R-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 B2 integrin receptor is critical for PMN-mediated endothelial injury.
Koike
K
K
Department of Surgery, Denver General Hospital and the University of Colorado Health Sciences Center, Denver Colorado.
Moore
E E
EE
Moore
F A
FA
Franciose
R J
RJ
Fontes
B
B
Kim
F J
FJ
D000818:Animals; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000150:complications; D008168:Lung / Q000276:immunology*; D008171:Lung Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D016177:Macrophage-1 Antigen / Q000627:therapeutic use*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury / Q000150:complications*
D016177:Macrophage-1 Antigen; D009195:Peroxidase