A New Function for an Old Enzyme: The Role of DNase I in Apoptosis

Programmed cell death or apoptosis (Greek for the falling of the leafs in autumn) is an event by which cells are deliberately eliminated (recently reviewed by Ucker 1991, Williams et al. 1992 and Cohen 1993). It occurs during embryogenesis, during the formation of digits from a limb bud, during the selection of immunocompetent B or autoreactive T cells, and in many tissues to provide a stable balance of cellular mass. The morphologic events during apoptosis differ from those of necrosis, defined as the dying of cells by plasma membrane injury. During apoptosis, the nuclear chromatin rapidly condenses to form crescent-shaped deposits along the nuclear envelope. The nucleus convolutes and fragments, while the cytoplasmic membrane forms protuberances. These are subsequently released forming so-called apoptotic bodies containing highly condensed DNA. The whole cell may disintegrate into a large number of membrane-sealed apoptotic bodies which are immediately phagocytosed by neighboring cells or macrophages. Apoptosis affects only single cells dispersed in a given tissue and there is no release of cytoplasmic contents into the extracellular space and therefore no inflammatory reaction is induced. In contrast, necrotic cell death usually affects a large number of neighboring cells. Due to the membrane injury, cytoplasmic contents leak into the extracellular space and an inflammatory reaction ensues.