Yamamoto Y, Klein T W, Tomioka M, Friedman H
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612, USA.
Cell Immunol. 1997 Feb 25;176(1):75-81. doi: 10.1006/cimm.1996.1074.
It has been reported that granulocyte/macrophage colony-stimulating factor (GM-CSF), one of the hemopoietic growth factors which regulates the function of phagocytic cells, is a potent activator of cultured macrophages and induces antimicrobial activities as well as differentiation of precursor cells. In this study, we examined the ability of recombinant murine GM-CSF to activate mouse peritoneal macrophages to restrict the growth of two different microorganisms, Candida albicans and Legionella pneumophila, both of which are important opportunistic pathogens in an immunocompromised host. Treatment of thioglycollate-elicited BDF1 mouse macrophages with GM-CSF for 24 hr enhanced the anti-C. albicans activity of the macrophages in terms of inhibiting growth of the fungi. Reactive oxygen (H2O2) and IL-1 production by the macrophages were also enhanced by treatment with GM-CSF. However, no enhancement of anti-L. pneumophila activity of macrophages obtained from either susceptible A/J or resistant BDF1 mice to L. pneumophila infection after treatment with up to 1000 units/ml GM-CSF was observed under the same conditions. When the treatment time was extended to 72 hr. GM-CSF was still unable to induce anti-L. pneumophila activity. As a control study, treatment with recombinant IFN-gamma enhanced both anti-Candida and anti-Legionella activity in cultured macrophages under the same conditions used in the GM-CSF study. Measurement of cellular iron content revealed the low iron content in IFN-gamma-treated macrophages, but no decrease of iron in GM-CSF-treated macrophages compared with the control group, indicating a possible involvement of iron as a key factor in anti-L. pneumophila activity. Thus, the results of the study show that GM-CSF activation of elicited peritoneal macrophages is selective with regard to the type of antimicrobial activity induced.
据报道，粒细胞/巨噬细胞集落刺激因子（GM-CSF）作为调节吞噬细胞功能的造血生长因子之一，是培养巨噬细胞的有效激活剂，可诱导抗菌活性以及前体细胞的分化。在本研究中，我们检测了重组鼠GM-CSF激活小鼠腹腔巨噬细胞以限制两种不同微生物生长的能力，这两种微生物分别是白色念珠菌和嗜肺军团菌，它们在免疫受损宿主中均为重要的机会致病菌。用GM-CSF处理巯基乙酸诱导的BDF1小鼠巨噬细胞24小时，增强了巨噬细胞对白色念珠菌的抗真菌活性，表现为抑制真菌生长。GM-CSF处理还增强了巨噬细胞活性氧（H2O2）的产生和白细胞介素-1的分泌。然而，在相同条件下，用高达1000单位/毫升的GM-CSF处理后，无论是对嗜肺军团菌易感的A/J小鼠还是抗性的BDF1小鼠来源的巨噬细胞，均未观察到抗嗜肺军团菌活性增强。当处理时间延长至72小时时，GM-CSF仍无法诱导抗嗜肺军团菌活性。作为对照研究，在GM-CSF研究中使用的相同条件下，用重组干扰素-γ处理可增强培养巨噬细胞的抗念珠菌和抗军团菌活性。细胞铁含量测定显示，干扰素-γ处理的巨噬细胞中铁含量较低，但与对照组相比，GM-CSF处理的巨噬细胞中铁含量没有降低，这表明铁可能是抗嗜肺军团菌活性的关键因素。因此，该研究结果表明，GM-CSF对诱导的腹腔巨噬细胞的激活在诱导的抗菌活性类型方面具有选择性。
