McLaughlin L, Zhu G, Mistry M, Ley-Ebert C, Stuart W D, Florio C J, Groen P A, Witt S A, Kimball T R, Witte D P, Harmony J A, Aronow B J
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575, USA.
J Clin Invest. 2000 Nov;106(9):1105-13. doi: 10.1172/JCI9037.
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.
载脂蛋白J/簇集素（apoJ/簇集素）是一种功能未知但引人关注的蛋白质，在心肌炎及许多其他炎症性损伤中被诱导产生。为了测试其改变肌球蛋白诱导的自身免疫性心肌炎的能力，我们培育了apoJ基因缺陷小鼠。apoJ基因缺陷小鼠和野生型小鼠心肌炎的初始发病情况相似，这一点通过T细胞介导的免疫反应的两个早期标志物——主要组织相容性复合体II类分子（MHC-II）和肿瘤坏死因子受体p55的诱导得以证明。此外，针对主要抗原心肌肌球蛋白的自身抗体诱导程度相同。尽管相同比例的受攻击动物都出现了一定程度的炎性浸润，但apoJ基因缺陷动物的炎症更为严重。apoJ基因缺陷小鼠的炎性病变更弥散、更广泛，尤其是在雌性小鼠中。与野生型动物形成鲜明对比的是，apoJ基因缺陷小鼠中针对心脏抗原的强烈全身性二次反应的发展预示着严重心肌炎。对二次抗原产生强烈抗体反应的野生型小鼠似乎受到保护，未发生严重炎症。炎症消退后，apoJ基因缺陷小鼠（而非野生型小鼠）出现心脏功能损害和严重心肌瘢痕形成。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。
