bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages.
Neutrophils, the most common inflammatory leukocytes, have the most limited life span of all blood cells. After they undergo apoptosis, they are recognized and engulfed by macrophages. bcl-2, a proto-oncogene rearranged and deregulated in B cell lymphomas bearing the t(14;18) translocation, is known to inhibit programmed death. bcl-2 expression is localized in early myeloid cells of the bone marrow but is absent in mature neutrophils. Transgenic mice that expressed bcl-2 in mature neutrophils showed that bcl-2 blocked neutrophil apoptosis. Despite this, homeostasis of neutrophil population is essentially unaffected. In fact, macrophage uptake of neutrophils expressing bcl-2 still occurred. This transgenic model indicates that the mechanism that triggers phagocytosis of aging neutrophils operates independently of the process of apoptosis regulated by bcl-2.
Lagasse
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Department of Pathology and Developmental Biology, Stanford University School of Medicine, California 94305.
Weissman
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D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001853:Bone Marrow / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D016393:Lymphoma, B-Cell; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D010587:Phagocytosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D013154:Spleen / Q000378:metabolism
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011505:Protein-Tyrosine Kinases