Neutrophil apoptosis in the lung after hemorrhage or endotoxemia: Apoptosis and migration are independent of IL-1 beta

Hemorrhage and endotoxemia are associated with neutrophil accumulation in t he lungs and the development of acute inflammatory lung injury. Because alt ernations in the rate of apoptosis may affect the number and function of ne utrophils in the lungs, we determined the percentage of neutrophils undergo ing apoptosis in the lungs of control, hemorrhaged, or endotoxemic mice. In control mice, 18.5 +/- 1.2% of pulmonary neutrophils were apoptotic. The p roportion of apoptotic neutrophil sin the lungs was significantly decreased 1 h after hemorrhage (6.5 +/- 1.6%, P < 0.01 compared to control) or endot oxemia (7.0 +/- 0.9%, P < 0.01 compared to control). Between 1 and 24 h aft er endotoxemia or hemorrhage, the proportion of apoptotic neutrophils in th e lung remained significantly depressed compared to that in control, unmani pulated mice. By 48 h, the proportion of apoptotic neutrophils returned to baseline levels in the lungs of hemorrhaged (21.4 +/- 1.4%) or endotoxemic (16.4 +/- 1.6%) mice. Lung neutrophil IL-1 beta mRNA was significantly incr eased from that of control mice [i.e., 0.12 +/- 0.06 relative absorbance un its (RAU)] 1 h after hemorrhage (5.19 +/- 0.068 RAU, P < 0.05 compared to c ontrol) or endotoxemia (8.90 +/- 1.53 RAU, P < 0.01 compared to control). I n IL-1 beta-deficient mice, there was no significant difference in lung neu trophil apoptosis or neutrophil entry into the lung after hemorrhage or end otoxemia compared to wild-type mice. Our results show that apoptosis among lung neutrophils is decreased for more than 24 h after hemorrhage or endoto xemia. Although IL-1 beta expression is increased in lung neutrophils under these conditions, IL-1 beta is not responsible for either the influx of ne utrophils into the lung or the reduction of apoptosis in neutrophil populat ions after hemorrhage or endotoxemia. (C) 1999 Academic Press.