Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis
Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis
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DOI：
10.1172/jci9037
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发表时间：
2000-11-01
影响因子：
15.9
通讯作者：
Aronow, BJ
中科院分区：
文献类型：
--
作者：
Mclaughlin, L;Zhu, G;Aronow, BJ
载脂蛋白J/簇蛋白（apoJ/clusterin）是一种功能未知的蛋白质，在心肌炎和许多其他炎症损伤中被诱导。为了测试其修饰肌球蛋白诱导的自身免疫性心肌炎的能力，我们产生了apoJ缺陷小鼠。ApoJ缺陷型小鼠和野生型小鼠表现出相似的心肌炎初始发作，如通过诱导T细胞介导的免疫应答的两个早期标志物MHC-II和TNF受体p55所证明的。此外，对主要抗原心肌肌球蛋白的自身抗体诱导到相同的程度。尽管相同比例的受攻击动物表现出一定程度的炎症浸润，但apoJ缺陷动物的炎症更严重。在apoJ缺陷小鼠中，尤其是在雌性小鼠中，炎性病变更加弥漫和广泛。与野生型动物形成鲜明对比的是，apoJ缺陷小鼠对心脏抗原产生强烈的全身性继发性反应预示着严重的心肌炎。具有对第二抗原的强Ab应答的野生型小鼠似乎受到保护免于严重炎症。在炎症消退后，apoJ缺陷型而非野生型小鼠表现出心脏功能受损和严重的心肌瘢痕形成。这些结果表明，apoJ限制了自身免疫性心肌炎的进展，并保护心脏免受炎症后组织破坏。
Apolipoprotein J/clusterin (apoJ/clusterin), an intriguing protein with unknown function, is induced in myocarditis and numerous other inflammatory injuries. To test its ability to modify myosin-induced autoimmune myocarditis, we generated apoJ-deficient mice. ApoJ-deficient and wild-type mice exhibited similar initial onset of myocarditis, as evidenced by the induction of two early markers of the T cell-mediated immune response, MHC-II and TNF receptor p55. Furthermore, autoantibodies against the primary antigen cardiac myosin were induced to the same extent. Although the same proportion of challenged animals exhibited some degree of inflammatory infiltrate, inflammation was more severe in apoJ-deficient animals. Inflammatory lesions were more diffuse and extensive in apoJ-deficient mice, particularly in females. In marked contrast to wild-type animals, the development: of a strong generalized secondary response against cardiac antigens in apoJ-deficient mice was predictive of severe myocarditis. Wild-type mice with a strong Ab response to secondary antigens appeared to be protected from severe inflammation. After resolution of inflammation, apoJ-deficient, but not wild-type, mice exhibited cardiac function impairment and severe myocardial scarring. These results suggest that apoJ limits progression of autoimmune myocarditis and protects the heart from postinflammatory tissue destruction.