T Terashima, M Kanazawa, K Sayama, T Urano, F Sakamaki, H Nakamura, Y Waki, K Soejima, S Tasaka and A Ishizaka
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.

We investigated the roles of neutrophils in mediating both the protective 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 following the intratracheal instillation of Pseudomonas aeruginosa in low (10(4) colony-forming units [CFU]) and high doses (10(8) CFU) in normal (control) guinea pigs, others made neutropenic with cyclophosphamide (CPA), and guinea pigs made neutrophilic with recombinant granulocyte colony-stimulating factor (rG-CSF). Lung injury was assessed by the ratio of the concentration of 125I-labeled albumin in lung tissue to 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 ratio 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 were recovered from bronchoalveolar lavage fluid (BALF) in the CPA group. Neutrophil recruitment was observed in the lungs of animals in the control and rG-CSF groups. With 10(8) CFU, the mortality rate was increased 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 mortality during high-level bacterial challenge.

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