Published online before print August 30, 2001, doi: 10.1161/hh1801.096263
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© 2001 American Heart Association, Inc.
Integrative Physiology |
Fc Receptor–Mediated Inhibitory Effect of Immunoglobulin Therapy on Autoimmune Giant Cell Myocarditis
Concomitant Suppression of the Expression of Dendritic Cells
From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Correspondence to Chiharu Kishimoto, MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail kkishi{at}kuhp.kyoto-u.ac.jp
Abstract — In the present study, the mechanisms and importance of the Fc portion of immunoglobulin in experimental giant cell myocarditis were examined. Giant cell myocarditis was induced in rats by immunization of porcine cardiac myosin. Human intact immunoglobulin (1 g · kg-1 · d-1) or F(ab')2 fragments of human immunoglobulin (1 g · kg-1 · d-1) were administered intraperitoneally daily on days 1 to 21. Intact immunoglobulin administration significantly ameliorated myocarditis, but F(ab')2 fragments did not. The ribonuclease protection assay revealed that therapy with intact immunoglobulin, but not F(ab')2 fragments, suppressed the mRNA expressions of inflammatory and proinflammatory cytokines. Immunohistochemical analysis showed that therapy with intact immunoglobulin, but not F(ab')2 fragments, suppressed dendritic cell (DC) expression during both the early and the subsequent fulminant phases. Moreover, the early treatment of intact immunoglobulin until the 11th day or 14th day, when the expression of DCs was completely suppressed, ameliorated myocarditis. However, the late treatment of intact immunoglobulin beginning on day 15, when the expression of DCs had already been completed, failed to ameliorate the condition. An in vitro study showed that intact immunoglobulin, but not F(ab')2 fragments, suppressed the lipopolysaccharide-induced interleukin-1ß production associated with the downregulation of CD32 antigen (Fc
receptor II) expression. Thus, intact immunoglobulin therapy markedly suppressed myocarditis as a result of Fc receptor–mediated anti-inflammatory action, and the suppression of the disease was associated with the suppression of DCs, ie, the suppression of the initial antigen-priming process in experimental giant cell myocarditis.
Key Words: myocarditis • immunoglobulin • dendritic cells • cytokines • Fc receptors
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