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Contribution of neutrophils in lung defense for infection and in the pathogenesis of lung tissue injury.

中性粒细胞在肺感染防御和肺组织损伤发病机制中的贡献。

基本信息

批准号：
06670629
负责人：
KANAZAWA Minoru
金额：
$ 1.34万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

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.

我们研究了中性粒细胞在介导细菌感染的保护作用和铜绿假单胞菌（P.a.）在豚鼠身上。环磷酰胺预处理组支气管肺泡灌洗液（BALF）中回收活菌。对照组和嗜中性粒细胞集落刺激因子（G-CSF）组动物肺内可见中性粒细胞募集。在10^8菌落形成单位（CFU）P.a.，与对照组和血小板减少组相比，嗜肺组的死亡率增加，这反映了肺重量增加，表明严重的肺损伤。我们的结论是中性粒细胞在低水平细菌攻击时保护肺免受损伤，但在高水平细菌攻击时增强肺损伤并导致死亡，然后我们研究了体外G-CSF对单核细胞释放肿瘤坏死因子（TNF）的影响。外周血单核细胞和嗜中性粒细胞获自健康供体（n=8）。单独的中性粒细胞、单独的单核细胞和中性粒细胞加单核细胞与和不与G-CSF一起孵育，并研究TNF释放。中性粒细胞单独不产生TNF脂多糖（LPS）刺激后，无论G-CSF治疗。在中性粒细胞存在的情况下，G-CSF预处理可抑制LPS刺激单核细胞释放TNF（P<0.01）。在单独的单核细胞中未观察到LPS后TNF释放的抑制。当单核细胞与来自G-CSF激活的中性粒细胞的上清液孵育时，LPS后单核细胞的TNF释放不受抑制。流式细胞术检测表明，G-CSF预处理也抑制了LPS刺激的单核细胞内TNF的产生（p<0.05）。这些数据表明，由G-CSF激活的中性粒细胞直接抑制由LPS刺激的单核细胞的TNF释放。