Apoptosis: a gene-directed programme of cell death.
Apoptosis is a particular type of programmed cell death which commonly occurs in the developing embryo, in normal healthy adult tissues and in many pathological settings. In contrast to necrosis, apoptosis is not a passive phenomenon but is gene-directed, usually requiring ongoing protein synthesis. The dying cell is characterised by having a raised level of cytosolic Ca2+; this activates a non-lysosomal Ca(2+)- and Mg(2+)-dependent endonuclease which digests the chromatin into oligonucleosome length fragments. The dying cell may or may not fragment into a number of apoptotic bodies, but in all cases the cell contents are bounded by a membrane which prevents the spillage of harmful substances such as DNA. Apoptotic cells are eliminated through phagocytosis by neighbouring cells and macrophages, and cell surface changes on apoptotic cells aid their recognition and engulfment by the phagocytosing cells. Extrinsic signals can both stimulate and inhibit apoptosis, and even direct damage to the cell can activate the process. Apoptosis is widely involved in organ formation in the embryo, and its occurrence in response to noxious stimuli such as cytotoxic drugs, irradiation and hyperthermia may be viewed as an altruistic suicide. Apoptosis provides a safe disposal mechanism for neutrophils at inflamed sites, and within the immune system it is considered responsible for eliminating self-reactive T-cell clones and for the affinity maturation of antibody producing cells. A failure to undergo apoptosis has been invoked in the pathogenesis of low-grade follicular lymphoma, and the triggering of apoptosis with monoclonal antibodies specifically in tumour cells has been achieved in one or two cases.
Alison
M R
MR
Royal Postgraduate Medical School, London.
Sarraf
C E
CE
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D016923:Cell Death / Q000235:genetics* / Q000276:immunology; D004247:DNA / Q000032:analysis; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008598:Menstruation / Q000235:genetics; D008854:Microscopy, Electron; D009336:Necrosis / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis; D051381:Rats; D014463:Ultrasonography
D000970:Antineoplastic Agents; D004247:DNA; D004720:Endonucleases