Kodama M, Matsumoto Y, Fujiwara M, Zhang S S, Hanawa H, Itoh E, Tsuda T, Izumi T, Shibata A
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
Circ Res. 1991 Oct;69(4):1042-50. doi: 10.1161/01.res.69.4.1042.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
巨细胞性心肌炎是一种严重且常致命的炎症性心脏病,其病因尚不清楚。在本研究中,我们利用实验模型研究了心肌炎中多核巨细胞的起源。我们还研究了与心肌炎中巨细胞形成相关的因素。通过在完全弗氏佐剂中用心肌肌凝蛋白免疫Lewis大鼠,诱导出以多核巨细胞出现为特征的严重心肌炎。在这种心肌炎中观察到两种类型的巨细胞,即异物巨细胞样和肌细胞样。免疫组织化学研究显示,这两种类型的多核巨细胞均被OX42和ED1(巨噬细胞标志物)染色,而未被抗结蛋白抗体和HHF35(肌纤维标志物)染色。因此,这种心肌炎中的多核巨细胞很可能来源于巨噬细胞。在疾病过程中,多核巨细胞的出现仅限于与炎症暴发性阶段相对应的时期。当通过用不同剂量的抗原免疫来调节疾病的严重程度时,多核巨细胞仅在接种大剂量抗原后出现的严重心肌炎中出现。免疫佐剂的使用也影响巨细胞的形成。大多数在完全弗氏佐剂中注射心肌肌凝蛋白的大鼠发生了巨细胞性心肌炎。(摘要截短于250字)