NEUTROPHIL SHORT-LIVED OXIDANT PRODUCTION - ENHANCEMENT FOLLOWING ONSET OF SEPSIS-INDUCED LUNG INJURY

Generation of superoxide anion (O2-) by activated neutrophils (PMN) is implicated in the pathogenesis of endothelial cell injury in sepsis. To quantitate this phenomenon we studied the kinetics of O2- productio n by PMN following in vivo and in vitro exposure to Pseudomonas aerugi nosa. PMN were isolated from young swine before and after a 1-hr infus ion with 5 x 10(8) organisms/ml at 0.3 ml/20 kg/min. Baseline PMN were studied in an in vitro system where 1 x 10(6) porcine PMN were incuba ted with live Pseudomonas for 1 hr at 37-degrees-C. Neutrophils from s eptic pigs exhibited a significantly increased (P < 0.05) initial rate of O2-production, which was 125% greater at 2 min following initial s timulation than saline control (P < 0.001). Neutrophils exposed in vit ro displayed a similar enhancement of the rate of O2-production; howev er, the rate was 3.6 times greater than that noted in vivo. The in viv o change in PMN oxidant generation was associated with a rise in both extravascular lung water (EVLW) and increased bronchoalveolar lavage p rotein (BAL-P) content. These data suggest that sepsis-induced acute l ung injury is accompanied by "priming" of circulating PMN; however, im portant factors are present in the circulation in sepsis that serve to attenuate the damaging potential of PMN oxidant species.