Abstract
The precise mechanism of myosin-induced autoimmune myocarditis is unknown. The purpose of the present study was to define the immunohistological and ultrastructural characteristics of the infiltrating cells, especially in the initial phase of the myocarditis. It was demonstrated that OX6-positive dendritic cells first infiltrated the cardiocytes on day 13 after immunization. After day 17, OX6-positive cells, which possessed elongated irregular-shaped processes on the cell surface but contained few phago-lysosomes in the cytoplasm, were located at the margin of an inflammatory field and inserted their processes into the sarcoplasm of cardiocytes. The central portion of the inflammatory field was occupied by ED1-positive inflammatory macrophages, which were rich in phagosomes and which were in contact with degenerating cardiocytes. No evidence was obtained which suggested that lymphocytes directly injured the cardiocytes. These results demonstrated ultrastructural evidence that the type of infiltrating cell that first injures cardiocytes is the cardiac dendritic cell. Inflammatory macrophages thereafter serve as scavengers of degenerating cardiocytes.
Similar content being viewed by others
References
Choti M, Lenrow D, Markmann J, Naji A (1989) Prolongation of cardiac allograft survival by pretreatment administration of cyclosporine and donor-specific dendritic cells. Transplant Proc 21:478–479
Darden AG, Clarke RD, Guttmann RD (1987) Rat cardiac dendritic cells: frequency in bred and congeneic rats. Transplant Proc 19:208
Darden AG, Clarke Forbes RD, Darden PM, Guttmann RD (1990) The effects of genetics and age on expression of MHC class II and CD4 antigens on rat cardiac interstitial dendritic cells. Cell Immunol 126:322–330
Hart DJN, Fabre JW (1981) Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med 153:347–361
Huber SA, Lodge PA (1984) Coxsackievirus B-3 myocarditis in Balb/c mice. Evidence for autoimmunity to myocyte antigens. Am J Pathol 116:21–29
Kodama M, Matsumoto Y, Fujiwara M, Masani F, Izumi T, Shibata A (1990) A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction. Clin Immunol Immunopathol 57:250–262
Kodama M, Zhang H, Hanawa H, Shibata A (1992) Immunohistochemical characterization of infiltrating mononuclear cells in the rat heart with experimental autoimmune giant cell myocarditis. Clin Exp Immunol 90:330–335
Larsen CP, Morris PJ, Austyn JM (1990) Migration of dendritic leucocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection. J Exp Med 171:307–314
Maisch B (1985) Immunologic regulator andeffector mechanisms in myocarditis and perimyocarditis. Heart Vessels 1 [Suppl 1]:209–217
McKenzie JL, Beard MEJ, Hart DNJ (1984) The effect of donor pretreatment on interstitial dendritic cell content and rat cardiac allograft survival. Transplantation 38:371–376
McLennan IS (1993) Resident macrophages (ED2- and ED3-positive) do not phagocytose degenerating rat skeletal muscle fibres. Cell Tissue Res 272:193–196
Murakami U, Uchida K, Hiratsuka T (1976) Cardiac myosin from pig heart ventricle: purification and enzymatic properties. J Biochem 80:611–619
Neu N, Beisel KW, Traystman MD, Rose NR, Craig SW (1987) Autoantibodies specific for the cardiac myosin isoform are found in mice susceptible to coxsackievirus B3-induced myocarditis. J Immunology 138:2488–2492
Neu N, Pummerer C, Rieker T, Berger P (1993) T cells in cardiac myosin-induced myocarditis. Clin Immunol Immunopathol 68:107–110
Roake JA, Rao AS, Larsen CP, Hankins DF, Morris PJ, Austyn M (1993) Cytokine mediated of non-lymphoid dendritic cell migration. In: Kamperdijk et al (eds) Dendritic cells in fundamental and clinical immunology. Plenum Press, New York, pp 501–506
Rose NR, Herskowitz A, Neumann DA (1993) Autoimmunity in myocarditis: models and mechanisms. Clin Immunol Immunopathol 68:95–99
Seko Y, Shinkai Y, Kawasaki A, Yagita H, Okumura K, Takaku F, Yazaki Y (1991) Expression of perforin in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3. Circulation 84:788–795
Smith SC, Allen PM (1992) Expression of myosin-class II major histocompatibility complexes in the normal myocardium occurs before induction of autoimmune myocarditis. Proc Natl Acad Sci USA 89:9131–9135
Spencer SC, Fabre JW (1990) Characterization of the tissue macrophage and the interstitial dendritic cell as distinct leucocytes normally resident in the connective tissue of rat heart. J Exp Med 171:1841–1851
Steinger B, Klempnauer J, Wonigeit K (1984) Phenotype and histological distribution of interstitial dendritic cells in the rat pancreas, liver, heart, and kidney. Transplantation 38:169–175
Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9:271–296
Zhang J, Yu Z-X, Fujita S, Yamaguchi ML, Ferrans VJ (1993) Interstitial dendritic cells of the rat heart. Quantitative and ultrastructural changes in experimental myocardial infarction. Circulation 87:909–920
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Suzuki, K. A histological study on experimental autoimmune myocarditis with special reference to initiation of the disease and cardiac dendritic cells. Vichows Archiv A Pathol Anat 426, 493–500 (1995). https://doi.org/10.1007/BF00193173
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00193173