Neutrophil-induced lung protection and injury are dependent on the amount of Pseudomonas aeruginosa administered via airways in guinea pigs

Takeshi Terashima, Minoru Kanazawa, Koichi Sayama, Tetsuya Urano, Fumio Sakamaki, Hidetoshi Nakamura, Yasuhiro Waki, Kenzo Soejima, Sadatomo Tasaka, Akitoshi Ishizaka

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20 Citations (Scopus)


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 (104 colony- forming units [CFU]) and high doses (108 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 104 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 108 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.

Original languageEnglish
Pages (from-to)2150-2156
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Issue number6 I
Publication statusPublished - 1995 Dec
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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