Skip Navigation

European Heart Journal 1995 16(Supplement O):92-96; doi:10.1093/eurheartj/16.suppl_O.92
Copyright © 1995 by the European Society of Cardiology.
This Article
Right arrow Full Text (PDF)
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Khaw, B. A.
Right arrow Articles by Carles, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Khaw, B. A.
Right arrow Articles by Carles, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1995 The European Society of Cardiology

SR-Ca2+ATPase as an autoimmunogen in experimental myocarditis

B. A. Khaw*,{dagger},, J. Narula*,{dagger}, A. R. Sharaf{dagger}, P. D. Nicol{dagger}, J. F. Southern{dagger} and M. Carles*

* Center for Drug Targeting and Analysis, Bouve College of Pharmacy and Health Sciences, Northeastern University Boston, Massachusetts, U.S.A.
{dagger} Massachusetts General Hospital Boston, Massachusetts, U.S.A.

Ban-An Khaw, PhD, Director and George D.Behrakis Professor of Pharmaeutical Sciences, Center for Drug Targeting and Anaylysis, Bouve College of Pharmacy and Helath Health Sciences, Northeastern University, Boston, MA 02115, U.S.A.

The concept of autoimrnunity in the pathogenesis of myocarditis or dilated cardiomyopathy is gaining impetus. Since systolic functional impairment and subsequent recovery are frequently observed in myocarditis, we reasoned that the development of autoimrnunity to cardiac sarcoplasmic reticulum calcium ATPase (SR-Ca2+ ATPase), which could interfere with intracellular calcium regulation and therefore affect myocardial contractility, should lead to immune-mediated myocarditis in experimental animals.Murine monoclonal antibody 4C11-20.21 (IgM class) generated against canine cardiac SR-Ca2+ATPase inhibits the cardiac but not the skeletal ATPase activity. Immunization of CAF1/J mice with 4C11-20.21-affinity'-column-purified cardiac SR-ATPase produced a time-dependent induction of myocardial injury consistent with the diagnosis of myocarditis. Furthermore, the antibody 4C11-20.21 alone can induce myonecrosis in severe combined immunodeficiency (SCID) mice indicating a mechanism of cardiomyopathy independent of the cytotoxic T-cell mediated autoimmunopathy. Administration of 4C11-20.21 into immunocompetent CAF1/J mice resulted in minimal myocardial abnormality (40% with perivascular and/or interstitial mononuclear lymphoplasmacytoid aggregates, 10% with borderline myocarditis and 10% with lesions consistent with focal myocarditis). All control animals had normal hearts. Immunoperoxidase electron microscopic examination of the involved cardiac tissues showed antibody localization in the subsarcolemmal myotubular system and focal staining of the immediately adjacent sarcolemma in mice injected with 4C11-20.21 but not with 2C12.1B5.The time-dependent association between cardiac SR-Ca2+ATPase administration and development of myocardial lesions, as well as potentiated induction of myonecrosis with anti-cardiac SR-Ca2+ATPase antibody in SCID relative to immunocompetent mice, suggest a potential autoimmunopathogenic role of cardiac SR-Ca2+ ATPase in experimental myocarditis

Key Words: Experimental autoimmune-myocarditis • cardiac SR-Ca2+ATPase • monaclonal anti-cardiac SR-Ca2+ • ATPase antibody • autoantigen • pathogenesis


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.