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

Abstract

Hemorrhage and endotoxemia are associated with neutrophil accumulation in the lungs and the development of acute inflammatory lung injury. Because alterations in the rate of apoptosis may affect the number and function of neutrophils in the lungs, we determined the percentage of neutrophils undergoing apoptosis in the lungs of control, hemorrhaged, or endotoxemic mice. In control mice, 18.5 +/- 1.2% of pulmonary neutrophils were apoptotic. The proportion of apoptotic neutrophils in the lungs was significantly decreased 1 h after hemorrhage (6.5 +/- 1.6%, P < 0.01 compared to control) or endotoxemia (7.0 +/- 0.9%, P < 0.01 compared to control). Between 1 and 24 h after endotoxemia or hemorrhage, the proportion of apoptotic neutrophils in the lung remained significantly depressed compared to that in control, unmanipulated 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-1beta mRNA was significantly increased from that of control mice [i.e., 0.12 +/- 0.06 relative absorbance units (RAU)] 1 h after hemorrhage (5.19 +/- 0.068 RAU, P < 0.05 compared to control) or endotoxemia (8.90 +/- 1.53 RAU, P < 0.01 compared to control). In IL-1beta-deficient mice, there was no significant difference in lung neutrophil apoptosis or neutrophil entry into the lung after hemorrhage or endotoxemia compared to wild-type mice. Our results show that apoptosis among lung neutrophils is decreased for more than 24 h after hemorrhage or endotoxemia. Although IL-1beta expression is increased in lung neutrophils under these conditions, IL-1beta is not responsible for either the influx of neutrophils into the lung or the reduction of apoptosis in neutrophil populations after hemorrhage or endotoxemia.