Nitric oxide synthase induces macrophage death by apoptosis.
Stimulation processes effective for macrophage (M phi) cytostasis induction also led to a L-arginine-dependent M phi cell death by apoptosis in parallel to nitrite and citrulline production. Resident M phi stimulated with LPS plus IFN-gamma and MDP produced high amounts of nitrite and underwent apoptosis. Inflammatory M phi treated with LPS or IFN-gamma alone produced low levels of nitrite and were not apoptotic, whereas a synergistic effect was observed, the combined treatment leading to high amounts of nitrite and to apoptosis. Primed M phi obtained from concanavalin A-treated mice, after stimulation with LPS alone, released high amounts of nitrite and exhibited the typical ladder pattern of DNA fragmentation of apoptotic cells. In the three cases the L-arginine-dependent nitrite production was inhibited by NG-monomethyl-L-arginine, a competitive inhibitor of NO synthase, which moreover, also inhibited cell apoptosis. These findings and kinetics studies suggest the involvement of NO synthase in apoptosis induction.
Sarih
M
M
CNRS-URA 1116, Institut de Biochimie, Université Paris-Sud, Orsay, France.
Souvannavong
V
V
Adam
A
A
D000594:Amino Acid Oxidoreductases / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002956:Citrulline / Q000096:biosynthesis; D005260:Female; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism
D009573:Nitrites; D002956:Citrulline; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases