To elucidate the role of apoptosis in the disappearance of multinuclea
ted giant cells from the granulation tissue in cases of foreign-body g
ranuloma, we induced a foreign-body reaction by implanting a collagen
sponge into the dorsum of the rat and observed apoptotic changes withi
n the multinucleated giant cells using electron microscopy. Two types
of multinucleated giant cells were identified presenting apoptotic cha
racteristics morphologically. One was characterized by apoptosis of on
ly one nucleus, followed by cytoplasmic changes, rupture of the plasma
membrane and necrosis evoking an inflammatory reaction. The other sho
wed typical apoptotic changes in the majority or in all of the nuclei,
followed by phagocytosis of the apoptotic syncytia. The results of th
e present study suggest that apoptosis occurring within only one nucle
us might be triggered by overexpression of the p53 protein, because DN
A abnormalities are confined to this single nucleus. In contrast apopt
osis occurring simultaneously in the majority or all of the nuclei is
most probably due to cell death caused by senescence.