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Biochem Biophys Res Commun. 1993 Mar 15;191(2):503-8.

Nitric oxide synthase induces macrophage death by apoptosis.

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CNRS-URA 1116, Institut de Biochimie, Université Paris-Sud, Orsay, France.


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.

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