Influence of Apoptotic Bodies and Apoptotic Microvesicles on NO Production in Macrophages

We studied the effect of extracellular vesicular particles generated during apoptosis by macrophages of M0, M1 and M2 phenotypes on spontaneous and LPS-stimulated production of NO. The fractions of apoptotic bodies and apoptotic microvesicles were obtained in the primary cultures of peritoneal macrophages undergoing apoptosis. The effect of these microparticles on LPS-induced proinflammatory response of recipient macrophages critically depends on the initial phenotype of "donor" macrophages. Microvesicles and especially apoptotic bodies from M1 macrophages stimulate basal NO production. LPS stimulation of these macrophages preincubated with apoptotic bodies was not followed by further growth of NO production; in macrophages preincubated with microvesicles, LPS even suppressed NO production. Apoptotic microparticles obtained from M2 macrophages produced little effect on the basal production of NO. LPS stimulation of macrophages-recipients preincubated with microparticles from M2 macrophages did not enhance NO production. Incubation of macrophages with apoptotic microparticles induces the formation of endotoxic tolerance.

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