Mechanism of leukocyte infiltration in rheumatoid arthritis

类风湿性关节炎白细胞浸润机制

• 批准号: 04670214
• 负责人: KAMBARA Takeshi
• 金额: $ 1.34万
• 依托单位: Kumamoto 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: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670214/
• 关键词: Rheumatoid Arthritis; Chemotactic factor; Chemotaxis-inhibitory factor; MCP-1; IL-8; C5-derived factor; H-derived factor; 補体H因子由来因子; 絨毛組織; 関節液; Tリンパ球遊走因子; C4a

To elucidate the mechanism of leukocyte infiltration in rheumatoid arthritis, the chemotactic and chemotaxis-inhibitory factor were examined in rheumatoid synovial tissues and fluids. 1.Monocyte-chemotactic factor : Monocyte-chemotactic activities were determined in the extracts of rheumatoid synovial tissue using Boyden's chamber method and/or polarization assay. Strong chemotactic activities were detected in the extracts. Using HPLC, two fractions were obtained : one is of molecularweight aound 60,000, having specific activity for monocytes.The molecularweight was determined to be 45,000(MCP-45) by SDS disc electrophoresis. It has common antigenicity with C5 and was found to be identical with chemotactic factor in the normal serum which was produced by the action of factor XIII from C5. The other was of molecular weight 12,000(MCF-12) and was adsorbed by anti-MCP-1 antibody. 2.Monocyte-chemotaxis inhibitory factor : Chemotaxis-inhibitory factor which was specific for monocytes was found in the rheumatoid synovial fluids. The factor was found to be released from peripheral blood monocytes, U937 cells, and THP-1 cells after stimulated with C4a. The molecular weight was determined to be 20,000(MCIF-20), and was found to be different from C4a by adsorption experiment using anti-C4 anitbody. 3.T lympnocyte-chemotactic factor : T lymphocyte-chemotactic activity was found in the extracts of rheumatoid synovialtissues. The activity was fractionated into 2 by column chromatography. One was of molecular weight 67,000, but was chemokinetic. The other was of molecular weight 12,000(TCF-12), and was specific for rheumatoid arthritis and was not detected in the extracts of osteoarthritis. The activity was adsorbed by the anti-IL-8-affinity column. The factor has no T lympnocyte subset specificity. These lines of study were pertinent to elucidate the pathogenesis of rheumatoid arthritis.

为了阐明类风湿关节炎中白细胞浸润的机制，检测了类风湿关节炎滑膜组织和滑膜液中的趋化因子和趋化抑制因子。1.单核细胞趋化因子：采用Boyden’s小室法和/或极化法测定类风湿关节炎滑膜组织提取液中单核细胞趋化活性。提取物具有较强的趋化活性。用HPLC法分离得到两个组分：一个组分的分子量约为60，000，对单核细胞具有特异活性，SDS圆盘电泳法测得其分子量为45，000（MCP-45）。它与C5有共同的抗原性，并发现与正常血清中由C5的因子XIII作用产生的趋化因子相同。另一种分子量为12，000（MCF-12），被抗MCP-1抗体吸附。2.单核细胞趋化抑制因子：类风湿关节炎关节液中存在单核细胞特异性趋化抑制因子。发现该因子在用C4 a刺激后从外周血单核细胞、U937细胞和THP-1细胞中释放。分子量测定为20，000（MCIF-20），通过使用抗C4抗体的吸附实验发现其与C4 a不同。3. T淋巴细胞趋化因子：类风湿关节炎滑膜组织提取液中存在T淋巴细胞趋化活性。通过柱层析将活性分级为2。一个分子量为67，000，但具有化学动力学。另一种分子量为12，000（TCF-12），对类风湿性关节炎具有特异性，在骨关节炎提取物中未检测到。活性被抗IL-8亲和柱吸附。该因子无T淋巴细胞亚群特异性。这些研究线是相关的，以阐明类风湿关节炎的发病机制。

项目成果

Junko Tanaka: "T cell chemotactic activity of cytokine LD78:A comparative study with interleukin-8,a chemotactic factor for the T cell CD45RA^+ phenotype." Int.Arch.Allergy Immunol.100. 201-208 (1993)

Junko Tanaka：“细胞因子 LD78 的 T 细胞趋化活性：与白细胞介素 8（T 细胞 CD45RA^ 表型的趋化因子）的比较研究。”

Takahisa Imamura: "Role of thrombin and plasmin in the development of delayd hypersensitivity reaction in guinea pig skin." Inflammation. 16(2). 169-177 (1992)

Takahisa Imamura：“凝血酶和纤溶酶在豚鼠皮肤迟发性超敏反应发展中的作用。”

Takao Tsuruta: "Novel function of C4a anaphylatoxin : Release from monocytes of protein which inhibits monocyte chemotaxis" Am.J.Pathol.142(6). 1848-4857 (1993)

Takao Tsuruta：“C4a 过敏毒素的新功能：从单核细胞中释放抑制单核细胞趋化性的蛋白质”Am.J.Pathol.142(6)。

Hirokazu Ohtsuka: "Thrombin generates monocyte chemotactic activity from complement factor H." Immunology. 80. 140-145 (1993)

Hirokazu Ohtsuka：“凝血酶通过补体因子 H 产生单核细胞趋化活性。”

Junko Tanaka: "T cell chemotactic activity of cytokine LD78." Int.Arch.Allergy Immunol.100. 201-208 (1993)

Junko Tanaka：“细胞因子 LD78 的 T 细胞趋化活性。”