| Project/Area Number |
06670629
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
KANAZAWA Minoru Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (80118934)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZAKA Akitoshi Keio University, School of Medicine, Assistant, 医学部, 助手 (90176181)
TERASHIMA Takeshi Keio University, School of Medicine, Assistant, 医学部, 助手 (30227516)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Acute lung injury / Neutrophil / Lung infection / Monocyte / Granulocyte colony-stimulating factor / Pseudomonas aeruginosa / Tumoe necrosis factor / Guinea pig / 急性呼吸促進症候群 / 単核球 / エンドトキシン / 肺感染防御 / 肺損傷 / サイクロフォスファミド |
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| Research Abstract |
We investigated the roles of neutrophils in mediating both the protective effect against bacterial infection and the effect of lung injury induced after intratracheal instillation of Pseudomonas aeruginosa (P.a.) in guinea pigs. Viable bacteria were recovered from bronchoalveolar lavage fluid (BALF) in the neutropenic group pretreated with cyclophosphamide. Neutrophil recruitment was observed in the lungs of animals in the control group and neutrophilic group preteated with granulocyte colony-stimulating factor (G-CSF). With 10^8 colony forming unit (CFU) P.a., the mortality rate was increased in the neutrophilic group as compared with the control and the neutropenic groups, which was reflected an increased lung weight indicating severe lung injury. We conclude that neutrophils protect against lung injury during low-level bacterial challege, but enhance lung injury and contribute to mortality during high-level bacterial challenge.
We then investigated the in vitro effects of G-CSF on tumor necrosis factor (TNF) release from monocytes. Peripheral blood monocytes and neutrophils were obtained from healthy donors (n=8). Neutrophils alone, monocytes alone, and neutrophils plus monocytes were incubated with and without G-CSF and were studies for TNF release. Neutrophils alone did not produce TNF after lipopolysaccharide (LPS) stimulation irrespective of G-CSF treatment. TNF release after LPS from monocytes was suppressed by pretreatment with G-CSF in the presence of Neutrophils (P<0.01). The suppression of TNF release after LPS was not observed in the monocytes alone. TNF release from monocytes after LPS was not inhibited when monocytes were incubated with the supernatant from G-CSF-activated neutrophils. Preteatment with G-CSF also inhibited intracellular TNF production, as measured by flow cytometry, of monocytes stimulated by LPS (p<0.05). These data suggest that neutrophils activated by G-CSF directly suppress TNF release from monocytes stimulated by LPS.
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