Rheumatoid arthritis
Rheumatoid arthritis
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DOI：
10.1007/bf00915708
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发表时间：
1984-06
期刊：
影响因子：
5.1
通讯作者：
G. Weissmann;H. Korchak
中科院分区：
文献类型：
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作者：
G. Weissmann;H. Korchak
中性粒细胞占类风湿性关节炎（RA）患者滑液中发现的细胞的90%以上。由于这些液体还含有免疫复合物（IgG-IgG和IgG-IgM类风湿因子）和补体裂解产物（C5、C5 A、DES、ARG、C3 B等），所有反应物都存在于局部Arthus损伤中。此外，来自RA患者的中性粒细胞在体内和体外内吞这些免疫复合物和补体成分。因此，已经表明，溶酶体酶和中性粒细胞在摄取免疫复合物（在本体相中或在表面上）后释放的其他炎症介质至少部分地解释了类风湿性炎症。引起组织损伤和产生活性氧（例如O2）的溶酶体水解酶（尤其是中性蛋白酶）的分泌是对多种促分泌素（包括免疫复合物和补体成分）的刺激分泌反应的一部分。然而，分泌和O2产生的途径是刺激特异性的，可以通过（a）动力学分析，（B）改变刺激，（c）使用不渗透试剂阻断离散反应来解剖以建立因果关系。嗜中性粒细胞还产生11-环氧合酶的产物（例如，PGE 2、TXA 2）和5-和15-脂氧合酶（单、二和三酯，LTB 4及其异构体）。然而，环加氧酶产物（TXA 2除外）单独作用不会引起炎症;事实上，它们抑制中性粒细胞、血小板、巨噬细胞和肥大细胞的功能。最有效的促炎剂还确定为花生四烯酸的产品是LTB 4。LTB 4是一种有效的Ca离子载体，一种强的化学引诱剂，诱导局部炎症，并激活中性粒细胞。
Neutrophils constitute over 90% of cells found in the synovial fluid of rheumatoid arthritis (RA) patients. Since such fluids also contain immune complexes (IgG-IgG and IgG-IgM rheumatoid factors) and complement split products (C5, C5A, DES, ARG, C3B, etc.), all of the reactants are present for a local Arthus lesion. Moreover, neutrophils from RA patients endocytose these immune complexes and complement components in vivo and in vitro. In consequence, it has been suggested that lysosomal enzymes and other mediators of inflammation released by neutrophils after uptake of immune complexes (in the bulk phase or on the surface) account, at least in part, for rheumatoid inflammation. Secretion of lysosomal hydrolases, especially neutral proteases, which provoke tissue injury and generation of reactive oxygen species (e.g. O2) is part of a stimulus-secretion response to a variety of secretagogues, including immune complexes and complement components. However, the pathways of secretion and O2generation are stimulus-specific and can be dissected to establish cause and effect relationships by (a) kinetic analysis, (b) varying the stimulus, (c) use of impermeant reagents to block discrete responses. Neutrophils also generate products of 11-cyclo-oxygenase (e.g., PGE2, TXA2) and of the 5- and 15-lipoxygenase (mono-, di-and trihetes, LTB4 and their isomers). However, the cyclo-oxygenase products (except TXA2) do not cause inflammation acting alone; indeed, they inhibit the function of neutrophils, platelets, macrophages and mast cells. The most potent proinflammatory agent yet identified as a product of arachidonate is LTB4. LTB4 is a potent Ca ionophore, a strong chemo-attractant, induces local inflammation, and activates neutrophils.