Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis

Apolipoprotein J/clusterin (apoJ/clusterin), an intriguing protein with unk nown function, is induced in myocarditis and numerous other inflammatory in juries. To test its ability to modify myosin-induced autoimmune myocarditis , we generated apoJ-deficient mice. ApoJ-deficient and wild-type mice exhib ited 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 r eceptor p55. Furthermore, autoantibodies against the primary antigen cardia c myosin were induced to the same extent. Although the same proportion of c hallenged animals exhibited some degree of inflammatory infiltrate, inflamm ation 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 gene ralized secondary response against cardiac antigens in apoJ-deficient mice was predictive of severe myocarditis. Wild-type mice with a strong Ab respo nse 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. Thes e results suggest that apoJ limits progression of autoimmune myocarditis an d protects the heart from postinflammatory tissue destruction.