STUDIES ON THE MECHANISMS FOR EXPRESSION OF THE SUPPRESSOR ACTIVITY BY MYCOBACTERIUM AVIUM COMPLEX-INDUCED IMMUNOSUPPRESSIVE MACROPHAGES

鸟分枝杆菌复合体诱导的免疫抑制巨噬细胞表达抑制活性的机制研究

基本信息

  • 批准号:
    10670255
  • 负责人:
  • 金额:
    $ 1.02万
  • 依托单位:
  • 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 2000
  • 项目状态:
    已结题

项目摘要

We studied profiles of cell-to-cell interaction of immunosuppressive macrophages (MΦs) induced by Mycobacterium avium complex infection (MAC-MΦs) with target T cells. First, experiments using a dual chamber system indicated that cell contact is required for full expression of the MΦ suppressor activity against concanavalin A (Con A)-induced T cell mitogenesis. MAC-MΦs displayed suppressor activity in an H-2 allele-independent manner, indicating that MHC molecules are not required for such cell contact. The suppressor activity of MAC-MΦs was markedly reduced by treatment with either paraformaldehyde, cytochalasin B, or colchicine, indicating that vital membrane functions of MAC-MΦs are required for the expression of suppressor activity. Second, blocking experiments using antibodies (Abs) against adhesion molecules indicated that B7-1 but none of B7-2, ICAM-1, or VCAM-1 molecules were required for expression of the MΦ suppressor activity. Indeed, MAC-MΦs displayed markedly increased B7-1 … More expression in parallel with the acquisition of the suppressor activity. Third, Ab-blocking of CD28 and CTLA-4 on target T cells did not reduce the suppressor activity of MAC-MΦs. Thus, there may exist another type of surface molecules on target T cells, that serves as a receptor for B7-1-mediated suppressive signals from MAC-MΦs. Fourth, precultivation of splenocytes (SPCs) with MAC-MΦs reduced Con A-induced mitogenesis but not phorbol myristate acetate (PMA)/Ca^<2+> ionophore A23187-elicited proliferation of the SPCs. Thus, when resting T cells receive suppressive signals from MAC-MΦs via cell contact and are subsequently subjected to a Con A stimulatory signal, MΦ-derived suppressor signals may interfere with the upstream events of protein kinase C(PKC) activation or intracellular Ca^<2+> mobilization. Indeed, Co-cultivation of splenic T cells with MAC-MΦs reduced Con A-induced PKC activation and its translocation to the cell membrane in the T cells. Fifth, when MAC-MΦs came in contact with T cells which had been subjected to PMA/A23187 signals, T cell proliferative response was strongly suppressed. Thus, when PMA/A23187-induced signal transduction events have already been mobilized in target T cells, MAC-MΦ suppressor signals can also cross-talk with the downstream pathways of PKC activation or Ca^<2+> mobilization. Less
我们研究了鸟分枝杆菌复合体(MAC-MΦ s)感染诱导的免疫抑制性巨噬细胞(MΦ s)与靶T细胞的细胞-细胞相互作用。首先,使用双室系统的实验表明,细胞接触是针对伴刀豆球蛋白A(Con A)诱导的T细胞有丝分裂的MΦ抑制剂活性的完全表达所必需的。MAC-MΦ以H-2等位基因非依赖性方式显示抑制活性,表明这种细胞接触不需要MHC分子。多聚甲醛、细胞松弛素B或秋水仙素处理后,MAC-MΦs的抑制活性显著降低,表明MAC-M Φs的重要膜功能是抑制活性表达所必需的。第二,使用抗粘附分子的抗体(Ab)的阻断实验表明,B7-1而不是B7-2、ICAM-1或VCAM-1分子对于MΦ抑制剂活性的表达是必需的。事实上,MAC-MΦ显示B7-1显著增加, ...更多信息 表达与抑制活性的获得平行。第三,Ab阻断靶T细胞上的CD 28和CTLA-4并不降低MAC-MΦs的抑制活性。因此,靶T细胞上可能存在另一种类型的表面分子,其充当B7-1介导的来自MAC-MΦ的抑制信号的受体。第四,用MAC-MΦs预培养脾细胞(SPC)可减少Con A诱导的有丝分裂,但不能减少佛波醇肉豆蔻酸酯(PMA)/Ca^2+载体A23187诱导的SPC增殖。因此,当静息T细胞通过细胞接触接收来自MAC-MΦs的抑制性信号并随后受到Con A刺激性信号时,MΦ衍生的抑制性信号可能干扰蛋白激酶C(PKC)激活或细胞内Ca^2+动员的上游事件。事实上,脾T细胞与MAC-MΦ的共培养减少了Con A诱导的PKC活化及其在T细胞中向细胞膜的移位。第五,当MAC-MΦ与已经经受PMA/A23187信号的T细胞接触时,T细胞增殖反应被强烈抑制。因此,当PMA/A23187诱导的信号转导事件已经在靶T细胞中被动员时,MAC-MΦ抑制信号也可以与PKC激活或Ca^2+动员的下游途径发生交叉。少

项目成果

期刊论文数量(39)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Tomioka H: "[Rview] Profiles of cytokine network in the hosts with mycobacterial infection.(in Japanese)"Clin.Immunol.. (in press). (2001)
Tomioka H:“[综述]分枝杆菌感染宿主细胞因子网络的概况。(日语)”Clin.Immunol..(正在出版)。
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    0
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冨岡治明: "らい菌感染宿主に誘導されるサイトカイン産生異常"臨床免疫. 33. (2000)
Haruaki Tomioka:“麻风分枝杆菌感染宿主中诱导的细胞因子异常产生”《临床免疫学》33。(2000)
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Shimizu Tosiaki: "Roles of tumor necrosis facter-α transforming growth factor-beta in regulating intercellular adehesion molecule-1 expression on murin peritoneal macrophages infected with Mycobacterium leprae." Intenationl Journal of Leprosy. (1999)
Shimizu Tosiaki:“肿瘤坏死因子-α 转化生长因子-β 在调节麻风分枝杆菌感染的鼠腹膜巨噬细胞中细胞间粘附分子-1 表达中的作用”(1999 年)。
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    0
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冨岡治明: "免疫抑制マクロファージ"臨床免疫. 33. 29-36 (2000)
Haruaki Tomioka:“免疫抑制巨噬细胞”临床免疫学 33. 29-36 (2000)。
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    0
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Sano Chiaki: "Effects of secretory leucocyte protease inhibitor on the production of the antiinflammatory cytokiens, IL-10 and transforming growth factor-beta(TGF-β), by lipopolysaccharide-stimulated macrophages."Clin Exp Immunol.. 121. 77-85 (2000)
Sano Chiaki:“分泌性白细胞蛋白酶抑制剂对脂多糖刺激的巨噬细胞产生抗炎细胞因子 IL-10 和转化生长因子-β (TGF-β) 的影响。”Clin Exp Immunol.. 121. 77-85 (2000)
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TOMIOKA Haruaki其他文献

TOMIOKA Haruaki的其他文献

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{{ truncateString('TOMIOKA Haruaki', 18)}}的其他基金

Development of new antituberculous drugs based on CoMFA 3D-QSAR analysis
基于CoMFA 3D-QSAR分析的抗结核新药开发
  • 批准号:
    23659506
  • 财政年份:
    2011
  • 资助金额:
    $ 1.02万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Molecular biological study on macrophage antimicrobial mechanism based on phospholipase A_2
基于磷脂酶A_2的巨噬细胞抗菌机制的分子生物学研究
  • 批准号:
    20591202
  • 财政年份:
    2008
  • 资助金额:
    $ 1.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study of virulence and drug-susceptabiltly of MAC strains isolated from Japanese patients with the nodular-bronchiectasis type MAC disease
日本结节性支气管扩张型 MAC 病患者 MAC 菌株毒力及药敏研究
  • 批准号:
    18590850
  • 财政年份:
    2006
  • 资助金额:
    $ 1.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Mechanisms of phospholipase A_2-dependent killing of microorganisms on macrophages
磷脂酶A_2依赖性巨噬细胞杀灭微生物的机制
  • 批准号:
    16590358
  • 财政年份:
    2004
  • 资助金额:
    $ 1.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Roles of free fatty acid macrophage mediated killing of mycobacteria
游离脂肪酸巨噬细胞介导的分枝杆菌杀伤作用
  • 批准号:
    13670272
  • 财政年份:
    2001
  • 资助金额:
    $ 1.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study on the roles of immunosuppressive cytokines in the establishment and progression of mycobacterial infections
免疫抑制细胞因子在分枝杆菌感染发生和进展中的作用研究
  • 批准号:
    07670310
  • 财政年份:
    1995
  • 资助金额:
    $ 1.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

identification of M.avium complex and exacerbation factor of pulmonary MAC disease by mass spectrometry
质谱法鉴定鸟分枝杆菌复合体及肺MAC疾病恶化因子
  • 批准号:
    15K19416
  • 财政年份:
    2015
  • 资助金额:
    $ 1.02万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Multiplex TB-M.avium complex Fluorescent in Situ hybridization Assay, direct from
多重 TB-M.avium 复合物荧光原位杂交检测,直接来自
  • 批准号:
    7749251
  • 财政年份:
    2009
  • 资助金额:
    $ 1.02万
  • 项目类别:
食細胞機能抑制マウスにおけるM.avium complex感染症の解析及び治療
吞噬功能抑制小鼠鸟分枝杆菌复合体感染的分析及治疗
  • 批准号:
    05670524
  • 财政年份:
    1993
  • 资助金额:
    $ 1.02万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
CD4欠損マウスにおけるM.avium complex(MAC)感染動態と解析と治療の開発
CD4 缺陷小鼠中鸟分枝杆菌复合体 (MAC) 感染动态和治疗的分析和发展
  • 批准号:
    04670465
  • 财政年份:
    1992
  • 资助金额:
    $ 1.02万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
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