Production and role of Macrophage activating factor (IFN-gamma) by bacterial lipopolysaccharide and other bacterial products

细菌脂多糖和其他细菌产物产生巨噬细胞激活因子（IFN-γ）及其作用

• 批准号: 61480149
• 负责人: NAKANO Masayasu
• 金额: $ 2.75万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480149/
• 关键词: Interferon-r; Bacterial lipopolysaccharide; LPS; Macrophage-activating factor; C3H; HeJ mouse; Beige mouse; BCG感作; 内毒素; ムラミールジペプチド; インターフェロン; BCG感染

(1) The cultured cells prepared from the spleens and peritoneal exudate cells of the C3H/HeJ strain of mice produce very little or no interferon (IFN) by stimulation of bacterial lipopolysaccharide (LPS). However, the cells taken from LPS-nonresponder C3H/Hej mice which had geen infected with mycobacterium bovis bacillus Calmette Guerin (BCG) prior to the experiment were capable of producing IFN in culture in the presence of LPS. The results in our experiments indicate that there is a mechanism of IFN- induction by LPS which rerquires the direct contact between adherent cells and nonadherent cells without the participation of any soluble factor(s) from the adherent cells. The producer cells were mainly in the nonadherent cell population. Previous treatment of nonadherent cells with anti-Thy 1.2, anti-Lyt-1.1, anti-L3T4, or anti-asialo-GMl antibody and complement diminished the ability of the cells for LPS-induced IFN production with the help of adherent cells. Therefore, it is concluded that both Tcells and natural killer cells in the BCG-primed C3H/Hej cell cultures produced IFN-gamma in the presence of LPS, and the production was supported by the function of macrophages.(2) we examined the effect of recombinant IFN-(gamma) on the bactericidal function in mice after the infection with virlent Salmonella enteritidis. Less than 1000 u of IFN could hardly show the effect. However, injection of 100 u IFN with 10 ng LPS revealed obviously bactericidal effect in the mice.(3) we examined the mechanisms of LPS-induced IL 1 production of macrophages and TSST-1-induced IL 2 prouction of T cells.

(1) C3H/HeJ小鼠脾细胞和腹膜渗出细胞经细菌脂多糖（LPS）刺激后产生干扰素（IFN）很少或不产生。然而，在实验之前，从感染了牛分枝杆菌卡介苗（BCG）的C3H/Hej小鼠身上提取的无LPS应答的细胞在LPS存在下能够产生IFN。我们的实验结果表明，LPS诱导IFN的机制需要贴壁细胞和非贴壁细胞之间的直接接触，而不需要贴壁细胞的任何可溶性因子的参与。产生细胞主要存在于非贴壁细胞群中。先前用抗thy 1.2、抗lyt -1.1、抗l3t4或抗asialo- gml抗体和补体治疗非贴壁细胞，在贴壁细胞的帮助下，降低了细胞产生lps诱导的IFN的能力。因此，我们得出结论，在LPS存在的情况下，bcg诱导的C3H/Hej细胞培养中的t细胞和自然杀伤细胞都能产生ifn - γ，并且巨噬细胞的功能支持了这种产生。(2)研究了重组干扰素-(γ)对肠炎沙门氏菌感染后小鼠杀菌功能的影响。小于1000u的IFN几乎没有效果。100 u IFN加10 ng LPS对小鼠有明显的杀菌作用。(3)探讨了lps诱导巨噬细胞产生IL -1和tsst -1诱导T细胞产生IL - 2的机制。

项目成果

T. Nitta, H. Konno-Ejiri, K. Nemoto, S. Okumura, A. Ozawa and M. Nakano: "The roles of interleukins in the synergistic effect of B-cell mitogens with concanavalin A on hydrocortisone-resistant thymic cell proliferation." Immunology. 59. 209-216 (1986)

T. Nitta、H. Konno-Ejiri、K. Nemoto、S. Okumura、A. Ozawa 和 M. Nakano：“白细胞介素在 B 细胞有丝分裂原与刀豆球蛋白 A 对氢化可的松耐药胸腺细胞增殖的协同作用中的作用

中野昌康: 病態生理. 5. 976-978 (1986)

中野正康：病理生理学。5. 976-978 (1986)

T. Nitta;H. Konno-Ejiri;K. Nemoto;S. Okumura;A. Oazawa;M. Nakano: Immunology. 59. 209-216 (1986)

T.新田；H.

T. Uchiyama, Y. Kamagata, X. Yan, M. Kohno, M. Yoshioka, H. Fujikawa, H. Igarashi, M. Okubo, F. Awano, T. Saito-Taki and M. Nakano: "Study of the biological activities of toxic shock syndrome toxin-1: IT. Induction of proliferative response and the interl

T. Uchiyama、Y. Kamagata、X. Yan、M. Kohno、M. Yoshioka、H. Fujikawa、H. Igarashi、M. Okubo、F. Awano、T. Saito-Taki 和 M. Nakano：“研究

M. Nakano and T. Nitta: and Immunopharmacology of Bacterial Endotoxin (Eds. by A. Szentivanyi and H. Friedman), Plenum Publishing Corporation, New York, N.Y.Sunergistic effect of endotoxin.with concanavalin A on DNA synthesis in lymphocytes and the role o

M. Nakano 和 T. Nitta：细菌内毒素的免疫药理学（A. Szentivanyi 和 H. Friedman 编辑），Plenum Publishing Corporation，纽约，纽约州。内毒素的 Sunergistic 作用。伴刀豆球蛋白 A 对淋巴细胞 DNA 合成的作用及其作用