NEUTROPHIL-INDUCED LUNG PROTECTION AND INJURY ARE DEPENDENT ON THE AMOUNT OF PSEUDOMONAS-AERUGINOSA ADMINISTERED VIA AIRWAYS IN GUINEA-PIGS

We investigated the roles of neutrophils in mediating both the protect ive effect against bacterial infection and the harmful effect of lung injury induced after the intratracheal instillation of live bacteria. We examined the mortality rate, lung injury, and bacterial clearance f ollowing the intratracheal instillation of Pseudomonas aeruginosa in l ow (10(4) colony-forming units [CFU]) and high doses (10(8) CFU) in no rmal (control) guinea pigs, others made neutropenic with cyclophospham ide (CPA), and guinea pigs made neutrophilic with recombinant granuloc yte colony-stimulating factor (rG-CSF). Lung injury was assessed by th e ratio of the concentration of I-125-labeled albumin in lung tissue t o that in plasma (T/P) and the animals' lung weight-to-body weight (LW /BW) ratio. With 10(4) CFU, the CPA group showed an increased T/P rati o of 0.22 +/- 0.03 versus 0.14 +/- 0.01 in the control and 0.11 +/- 0. 01 (mean +/- SEM) in the rG-CSF groups (p < 0.01). Viable bacteria wer e recovered from bronchoalveolar lavage fluid (BALF) in the CPA group. Neutrophil recruitment was observed in the lungs of animals in the co ntrol and rG-CSF groups. With 10(8) CFU, the mortality rate was increa sed in the rG-CSF group (7 of 10) as compared with the control (0 of 9 ) and CPA groups (1 of 9) (p < 0.05), which reflected an increased LW/ BW (g/kg) ratio (16 +/- 2 versus 12 +/- 1) in the CPA group (p < 0.05) . We conclude that neutrophils protect against lung injury during low- level bacterial challenge, but enhance lung injury and contribute to m ortality during high-level bacterial challenge.