Open AccessProtective effect of granulocyte colony‐stimulating factor (G‐CSF) in a granulocytopenic mouse model of Pseudomonas aeruginosa lung infection through enhanced phagocytosis and killing by alveolar macrophages through priming tumour necrosis factor‐alpha (TNF‐α) production
Author(s) -
SHIRAI R.,
KADOTA J.,
TOMONO K.,
OGAWA K.,
IIDA K.,
KAWAKAMI K.,
KOHNO S.
Publication year - 1997
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1997.4211317.x
Subject(s) - bronchoalveolar lavage , alveolar macrophage , immunology , phagocytosis , pulmonary alveolus , lung , pseudomonas aeruginosa , macrophage , tumor necrosis factor alpha , granulocyte , priming (agriculture) , granulocyte macrophage colony stimulating factor , cyclophosphamide , biology , microbiology and biotechnology , cytokine , medicine , respiratory disease , in vitro , bacteria , chemotherapy , biochemistry , genetics , germination , botany
We investigated the effects of G‐CSF in a granulocytopenic mouse model of Pseudomonas aeruginosa lung infection. The model was prepared by intratracheal instillation of the bacteria, while granulocytopenia was induced by intraperitoneal injection of 4.0 mg of cyclophosphamide (CPA). There was no difference in the survival rate between G‐CSF‐treated animals and the normal group, and the number of neutrophils in the blood and lung recovered to normal in the former group. However, the phagocytic and killing activities of neutrophils were lower in G‐CSF‐treated mice than in controls. Interestingly, the mortality rate increased significantly when anti‐TNF‐α antibody was combined with G‐CSF, although it was intermediate between CPA alone and CPA–G‐CSF‐treated mice. However, the improved mortality was not associated with a change in the number of neutrophils in the circulation and lung. Administration of anti‐TNF‐α antibody resulted in a significant suppression of TNF‐α in bronchoalveolar lavage fluid and of enhanced alveolar macrophage function (phagocytic and bactericidal activity) against P. aeruginosa in G‐CSF‐treated granulocytopenic mice. We showed also increased TNF‐α mRNA expression and TNF‐α production in vitro using G‐CSF‐pretreated alveolar macrophages compared with control untreated macrophages. Our results are the first evidence to suggest that G‐CSF provides a synergistic protective effect against lethal P. aeruginosa lung infection in the granulocytopenic host. This effect is probably due to enhancement of alveolar macrophage function through endogenous TNF‐α production, in addition to increasing the number of circulating neutrophils.