Multinucleated giant cells undergoing apoptosis in experimental autoimmune myocarditis.

This study used an experimentally induced myocarditis model in rats to demonstrate the formation and fate of multinucleated giant cells which are known to occur in different kinds of inflammatory lesions. Multinucleated giant cells were frequently recognized in the inflammatory foci, being intermingled with numerous ED1-positive inflammatory macrophages rich in phagosomes. The giant cells reacted with the ED1 antibody but not with ED2, and ultrastructurally resembled the inflammatory macrophages. Multinucleated giant cells possessing less than 5 nuclei in an ultrathin section were rich in phagosomes, whereas those with more nuclei contained numerous lipid droplets and only few phagosomes in their cytoplasm. Light microscopic observation of hematoxylin-eosin stained sections revealed that some multinucleated giant cells displayed variously sized dark bodies which likely corresponded to condensed and fragmented nuclear chromatin. Such multinucleated giant cells were positively stained with the TUNEL method. Under the electron microscope, all nuclei in one multinucleated giant cell showed an eccentric mass of homogeneously condensed chromatin. These observations suggest that multinucleated giant cells are formed by aggregation and also likely by fusion of inflammatory macrophages; gradually loosing the phagocytotic activity characteristic of the latter cells, they then die by apoptosis.