Alveolar neutrophils in endotoxin-induced and bacteria-induced acute lung injury in rats

Polymorphonuclear neutrophils (PMNs) are thought to play a major role in the pathogenesis of adult respiratory distress syndrome. Because the alveolar epithelium is a decisive factor in alveole-capillary wall permeability, a toxic effect of emigrated PMNs in alveolar spaces is conceivable. We evaluated alveolar PMN function in two rat models of acute lung injury induced by alveolar instillation of endotoxin [lipopolysaccharide (LPS)] or live Pseudomonas aeruginosa (PYO). Alveolar PMNs were isolated from bronchoalveolar lavage fluid 4 and 24 h after the challenge. Hypoxemia was assessed based on the ratio arterial partial pressure of O-2 (Pa-O2)/fraction of inspired O-2 (FIO2) during mechanical ventilation. The severity of lung injury in the two models was clearly different, since Pa-O2/FIO2 were approximate to 100 and approximate to 400 mmHg in PYO- and LPS-induced injuries, respectively. By contrast, alveolar neutrophil influx, unstimulated oxygen metabolite production, and proteinase (elastase, gelatinase B) secretions of ex vivo alveolar PMNs were not larger in the PYO model. Thus the difference in severity was not associated with variations in alveolar neutrophil recruitment or activation. Moreover, gelatinase and leukocyte elastase activities were absent in bronchoalveolar fluid, indicating effective antiproteinase defense in alveolar spaces. We conclude that alveolar neutrophils are not sufficient to create severe respiratory failure.