title: A physiologic role of Bcl-xL induced in activated macrophages.
abstract: Activated macrophages produce nitric oxide (NO) that is an important effector molecule for their antimicrobial and antitumor activities. Since this NO is also toxic for themselves, they have self-defense mechanisms. To elucidate the mechanisms in a physiologic condition, expression of bcl-2 family genes were examined in peritoneal macrophages and RAW264 macrophage cell line activated with IFN-gamma and LPS. Bcl-xL, but not bcl-2 and bax mRNA, was highly inducible within 3 h after stimulation. The induction required new protein synthesis, but was independent of effects of synthesized NO. Since activated RAW264 were more resistant to NO-induced apoptosis mediated by the exposure to S-nitroso-N-acetyl-penicillamine (SNAP) than nonactivated RAW264, the inducible Bcl-xL may play a role in the protection from NO toxicity. To confirm the protective function, RAW264 were stably transfected with bcl-xL. Those transfectants activated with IFN-gamma and LPS appeared highly resistant to NO-induced cell death detected within 24 h after stimulation, although their NO production was similar to those of parental RAW264 and neomycin control-transfected cells. Furthermore, bcl-xL transfectants displayed substantial protection from SNAP-induced apoptosis. These results establish a link between self-defense to the synthesized NO and the induction of Bcl-xL in activated macrophages.
authors.affiliation: Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Hatano
authors.forename: T
authors.initials: T
authors.lastname: Tokuhisa
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051020:bcl-X Protein
chemical_list: C494812:Bcl2l1 protein, mouse; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D009569:Nitric Oxide; D007371:Interferon-gamma