PMNs primed for superoxide release and increased CD11b expression do not sequester in normal lung.

Abstract

Our previous work has implicated platelet activating factor (PAF)-induced neutrophil (PMN) priming and increased CD11b/CD18 receptor expression in the pathogenesis of lung injury following gut ischemia/reperfusion (I/R). In this model CD11b blockade abrogates lung injury but does not alter PMN priming or pulmonary leukosequestration. We, therefore, hypothesized that PAF-stimulated PMN priming and CD11b expression are insufficient to promote lung PMN sequestration. Normal rat PMNs, labeled with 51Cr, were incubated with PAF (10 ng/ml) to induce priming for superoxide (O2-) generation and enhance CD11b expression. Gut I/R animals underwent superior mesenteric artery occlusion for 45 min. 51Cr-labeled PMNs (2 x 10(7)) were injected iv. Study groups, consisting of (a) normal/control, (b) sham/laparotomy, and (c) gut I/R, were given either normal or PAF-treated PMNs. PAF-primed PMNs had increased 2- release and CD11b expression, but did not sequester in the lungs of normal rats. However, following gut I/R PAF-treated PMNs sequestered in the pulmonary bed. These data suggest that PAF priming for O2- generation and increased CD11b expression are insufficient alone to promote PMN sequestration in the lung. Rather, additional factors generated by gut I/R are necessary for this process.