Mechanism of leukocyte infiltration in rheumatoid arthritis

为阐明类风湿关节炎中白细胞浸润的机制，对类风湿滑膜组织和滑液中的趋化因子和趋化抑制因子进行了检测。1.单核细胞趋化因子：用Boyden小室法和/或偏振法测定类风湿滑膜组织提取液中单核细胞趋化活性。在提取物中检测到较强的趋化活性。经高效液相色谱分离得到两个组分：一组分的相对分子质量约为60,000，对单核细胞具有比活性，经十二烷基硫酸钠圆盘电泳法测得其相对分子质量为45,000(MCP-45)。它与C5具有共同的抗原性，与C5因子XIII作用产生的正常血清中的趋化因子相同。另一种分子量为12,000(MCF-12)，可被抗MCP-1抗体吸附。2.单核细胞趋化抑制因子：类风湿滑液中存在单核细胞特异性趋化抑制因子。经C4a刺激后，外周血单核细胞、U937细胞和THP-1细胞均可释放该因子。用抗C4抗体进行吸附实验，确定其相对分子质量为20000(MCIF-20)，与C4a不同。3.T淋巴细胞趋化因子：类风湿滑膜组织提取液具有T淋巴细胞趋化活性。柱层析法将活性分离为2个组分。一种是分子量为67,000的，但具有化学动力学性质。另一种是分子量12,000(TCF-12)，专用于类风湿性关节炎，在骨关节炎的提取物中未检测到。活性用抗IL-8亲和层析柱吸附。该因子无T淋巴细胞亚群特异性。这些研究方向有助于阐明类风湿性关节炎的发病机制。

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.