Apoptosis in SLE--too little or too much?
Cells of the immune system are, most likely, programmed to die unless recruited into an immune response. An active cell death program may also be induced by a variety of soluble and surface signals, many of which have only recently been recognized. The importance of these pathways in maintaining tolerance is highlighted by the development of lupus-like diseases in three different mouse strains that have spontaneous mutations in the Fas/APO-1 receptor or its ligand. The known function of Fas/APO-1 in signalling apoptosis explains the persistence of self reactive cells in lpr mice although it is unclear, at present, whether Fas defects effect both central and peripheral tolerance. Whereas Fas/APO-1 receptor expression appears to be normal in humans with SLE, other defects in the Fas/APO-1 pathway or other key molecules in the cell death survival require further study.
Elkon
K B
KB
Specialized Center of Research (SCOR) in SLE, Hospital for Special Surgery, Cornell University Medical College, New York, NY 10021.
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D002470:Cell Survival; D006801:Humans; D007107:Immune System / Q000378:metabolism; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor
D000954:Antigens, Surface; D008024:Ligands; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor