Neutrophil recruitment and increased permeability during acute lung injuryinduced by lipopolysaccharide

The intranasal administration of lipopolysaccharide (LPS) to mice triggers a huge influx of polymorphonuclear neutrophils (PMNs) into the airway space s, with a peak at 48 h. The increase in protein concentration, an index of microvascular permeability, displayed a different pattern, i.e., a first in crease with a plateau between 3 and 24 h followed by a second increase peak ing at 72 h. When mice were depleted of circulating PMNs, the increase in p rotein concentration was inhibited at 3 h but not at 24 h. The lack of PMN involvement at 24 h was confirmed by 1) in situ activation of exudated PMNs present in the air spaces on intranasal administration of LPS and 2) induc tion of the migration of PMNs sequestered in lung vessels on intraperitonea l administration of LPS. These findings show that the increase in microvasc ular permeability during lung inflammation is due to at least two distinct mechanisms, an early one related to the neutrophil influx and a delayed one occurring even under neutropenic conditions.