Nitric Oxide Synthase Induces Macrophage Death by Apoptosis

doi:10.1006/bbrc.1993.1246

Biochemical and Biophysical Research Communications

Volume 191, Issue 2, 15 March 1993, Pages 503-508

https://doi.org/10.1006/bbrc.1993.1246 Get rights and content

Abstract

Stimulation processes effective for macrophage (MΦ) cytostasis induction also led to a L-arginine-dependent MΦ cell death by apoptosis in parallel to nitrite and citrulline production. Resident MΦ stimulated with LPS plus IFN-γ and MDP produced high amounts of nitrite and underwent apoptosis. Inflammatory MΦ treated with LPS or IFN-γ 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 MΦ obtained from concanavalinA-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 N^G-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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Citation Excerpt :
Apoptosis is a cellular mechanism that leads to different morphological and biochemical changes, such as caspase activation, ROS level increase, chromatin condensation, nucleosomal degradation and cell shrinkage (Forbes-Hernández et al., 2014). Many studies have demonstrated that LPS treatment is able to induce apoptosis in several cell types, including macrophages, by the secretion of TNFα and NO and the activation of different molecular pathways (Albina et al., 1993; Sarih et al., 1993; Murray et al., 1997; Xaus et al., 2000). For example, in macrophages and in human umbilical vein endothelial cells LPS has been shown to activate different caspases (Russe et al., 2014; Shioiri et al., 2009; Chakravortty et al., 2001), that in turn stimulate a series of MAP kinases, such as p-Erk1/2 and p38, involved in the promotion of inflammation (Ajizian et al., 1999; Carter et al., 1999 Heitmeier et al., 1998).
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Regular ArticleNitric Oxide Synthase Induces Macrophage Death by Apoptosis

Abstract

Regular Article
Nitric Oxide Synthase Induces Macrophage Death by Apoptosis