Differential expression of chemokines in inflammatory myopathies
Differential expression of chemokines in inflammatory myopathies
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DOI：
10.1212/wnl.58.12.1779
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发表时间：
2002-06-25
期刊：
影响因子：
9.9
通讯作者：
Schröder, JM
中科院分区：
文献类型：
--
作者：
De Bleecker, JL;De Paepe, B;Schröder, JM
背景：趋化因子是一类小分子细胞因子，在炎症反应中招募和激活炎症细胞。细胞毒性记忆T细胞和巨噬细胞侵袭非坏死肌纤维是多发性肌炎和散发性包涵体肌炎的特征。皮肌炎是一种补体介导的内皮病变。阐明引导淋巴细胞渗出和运输的机制可能导致选择性治疗干预。方法：使用识别白细胞介素-8、单核细胞趋化蛋白-1 （MCP-1）、MCP-3、胸腺和活化调节细胞因子TARC和正常t细胞表达和分泌的RANTES的非交叉反应抗体进行免疫印迹和多步骤免疫荧光研究，并使用适当的阳性和阴性对照。采用原位杂交技术定位MCP-1 mRNA。结果：在多发性肌炎和包涵体肌炎中，MCP-1蛋白在T细胞和巨噬细胞亚群上强烈表达，并积极侵袭一定比例的非坏死肌纤维。肌内膜炎症灶附近的毛细血管和小动脉对MCP-1有免疫反应，而在组织的未受影响部分MCP-1表达微弱或不表达。相比之下，皮肌炎患者的血管周和膜周内皮以及远离炎症浸润的部位广泛且强烈地表达MCP-1。在一些对照标本中，一小部分毛细血管也表达MCP-1，这可能反映了这种趋化因子在正常免疫监视中的作用。炎性肌病散在巨噬细胞中检测到MCP-1 mRNA。其他所有趋化因子均不存在。结论：趋化因子在炎性肌病症状期有差异表达。MCP-1在多发性肌炎和包涵体肌炎的肌细胞毒性中起主要作用。在皮肌炎中，MCP-1可能通过与内皮细胞结合的膜溶性攻击复合物而诱导。
Background: Chemokines represent a family of small-molecular-weight cytokines that recruit and activate inflammatory cells in response to inflammation. Invasion of cytotoxic memory T cells and macrophages in nonnecrotic muscle fibers characterizes polymyositis and sporadic inclusion body myositis. Dermatomyositis is a complement-mediated endotheliopathy. Elucidation of the mechanisms guiding lymphocyte diapedesis and trafficking could lead to selective therapeutic interventions. Methods: Immunoblots and multistep immunofluoreseence studies with non-cross-reactive antibodies recognizing interleukin-8, monocyte chemoattractant protein-1 (MCP-1), MCP-3, TARC (thymus and activation regulated cytokine), and RANTES (regulated upon activation, normal T-cell expressed and secreted), using appropriate positive and negative controls. In situ hybridization was used to localize MCP-1 mRNA. Results: MCP-1 protein was strongly expressed on T cells and a subset of macrophages actively invading a proportion of the nonnecrotic muscle fibers in polymyositis and inclusion body myositis alike. Capillaries and arterioles in the vicinity of endomysial inflammatory foci were immunoreactive for MCP-1, with faint or no expression in unaffected parts of the tissue. By contrast, widespread and strong endothelial MCP-1 expression occurred on perifascicular and perimysial endothelia in dermatomyositis, also at sites remote from inflammatory infiltrates. In some control specimens, a subset of capillaries also expressed MCP-1, possibly reflecting a role of this chemokine in normal immune surveillance. MCP-1 mRNA was detected in scattered macrophages in each inflammatory myopathy. All other chemokines were absent. Conclusion: Chemokines are differentially expressed in the symptomatic stage of inflammatory myopathies. MCP-1 plays a major role in the myocytotoxicity in polymyositis and inclusion body myositis. MCP-1 may be induced by membranolytic attack complex binding to endothelial cells in dermatomyositis.