CHARACTERISTICS OF GIANT-CELLS AND FACTORS RELATED TO THE FORMATION OF GIANT-CELLS IN MYOCARDITIS

Giant cell myocarditis is a serious and frequently fatal inflammatory heart disease of which the etiology remains unknown. In the present study, we investigated the origin of multinucleated giant cells in myocarditis with the use of an experimental model. We also examined the factors relating to the formation of giant cells in myocarditis. Severe myocarditis characterized by the appearance of multinucleated giant cells was induced in Lewis rats by immunization with cardiac myosin in complete Freund's adjuvant. Two types of giant cells, foreign body giant cell-like and myocytelike, were observed in this myocarditis. Immunohistochemical studies revealed that both types of multinucleated giant cells were stained with OX42 and ED1 (macrophage markers) and were not stained with anti-desmin antibody and HHF35 (markers for muscle fibers). Therefore, it is likely that multinucleated giant cells in this myocarditis are derived from macrophages. During the course of the disease, the appearance of multinucleated giant cells was restricted to a period corresponding with the fulminant phase of inflammation. When the severity of the disease was modulated by immunization with various doses of the antigen, multinucleated giant cells appeared only in severe myocarditis after inoculation of a large dose of the antigen. Administration of immunoadjuvants also affected the formation of giant cells. Most of the rats injected with cardiac myosin in complete Freund's adjuvant developed giant cell myocarditis. When rats were immunized with the antigen in incomplete Freund's adjuvant followed by a Bordetella pertussis injection, all the rats developed myocarditis without giant cells. Not only myocarditis but also the formation of giant cells was transferable into syngeneic rats with lectin-activated spleen cells taken from rats previously immunized with cardiac myosin in complete Freund's adjuvant. Based on these findings, strongly activated macrophages or T lymphocytes seem to be necessary for the generation of giant cell myocarditis.