A physiologic role of Bcl-xL induced in activated macrophages.
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.
Okada
S
S
Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Japan.
Zhang
H
H
Hatano
M
M
Tokuhisa
T
T
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
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