Analysis of the function of macrophages from mice infected with MADIDS.

MADIDS感染小鼠巨噬细胞的功能分析。

• 批准号: 10670438
• 负责人: YOSHIMOTO Tomohiro
• 金额: $ 1.98万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670438/
• 关键词: IL-18; MAIDS; macrophages; NK cells; MAIDS; NK細胞

IL-18, a product of activated macrophages and Kupffer cells, is a potent pleiotropic cytokine. IL-18 induces IFN-γproduction by lymphocytes, such as T cells, and natural killer (NK) cells, particularly in a synergistic manner with IL-12. IL-18 augments NK cell activity through the activation of constitutively express IL-18 receptor on NK cells. In addition, IL-18 upregulates Fas ligand-mediated cytotoxic activity of cloned Th1 cells and NK cells. IL-18 also directly activates CD8ィイD1+ィエD1T cells, which play a central role in viral clearance. Additionally, IL-18 as well as IL-12 is accumulated after infection with microbes or microbe products, allowing us to propose the possibility that IL-18 along with IL-12 participates in microbe clearance and furthermore exogenous IL-18 might enhance host defense. C57BL/6 mice inoculated with the mixture of murine leukemia viruses (MuL Vs) called LP-BM5 MuLV develop an immunodeficiency syndrome which in many ways resembles that seen in humans infected with human immunodecifiency virus type-1 (HIV-1). The function of macrophages and NK cells in HIV infection play a key role developing the diseases. Thus, we examined the function in mouse infected with LP-BM5 MuLV, murine AIDS (MAIDS). We also examined the contribution of IL-18 in developing of MAIDS. The results are following. First, we revealed that serum IL-18 was increased during the course of MAIDS, 〜5μg/ml at 16 weeks after infection . Second, macrophages from MAIDS which infected 8 weeks before produced IL-18 in response to LPS, while those from normal control C57BL/6 mice did not. Third, the expression of B7.2, as an activated cell surface marker on MAIDS macrophages was enhanced. Family, NK activity was augmented 8 weeks after infection with MAIDS.

IL-18是激活的巨噬细胞和库普弗细胞的产物，是一种强大的多效性细胞因子。IL-18诱导T细胞等淋巴细胞和自然杀伤细胞(NK细胞)产生干扰素-γ，特别是与IL-12协同作用。IL-18通过激活NK细胞上结构性表达的IL-18受体来增强NK细胞的活性。此外，IL-18上调Fas配体介导的克隆Th1细胞和NK细胞的细胞毒活性。IL-18还可直接激活CD8CD8ィイD1+ィエD1T细胞，这些细胞在病毒清除过程中起着核心作用。此外，IL-18和IL-12在感染微生物或微生物产物后积聚，这使得我们可以提出IL-18与IL-12一起参与微生物清除的可能性，此外，外源IL-18可能增强宿主防御。接种了名为LP-BM5MuLV的小鼠白血病病毒混合物的C57BL/6小鼠出现了一种免疫缺陷综合征，在许多方面与感染人类免疫决策病毒1型(HIV-1)的人类相似。巨噬细胞和NK细胞在HIV感染中的作用在疾病的发生发展中起着关键作用。因此，我们在感染LP-BM5MuLV的小鼠、小鼠艾滋病(女佣)中检测了其功能。我们还检测了IL-18在女佣发育中的作用。结果如下。首先，我们发现血清IL-18在女佣病程中升高，在感染后16周约为5μg/ml。其次，感染前8周感染的女佣巨噬细胞产生IL-18，而正常对照C57BL/6小鼠不产生IL-18。B7.2作为活化的细胞表面标志在MAIDES巨噬细胞上的表达增强。家系感染女佣后8周，NK活性增强。

项目成果

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