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

Ya Sh Schwartz1, O M Dolganova2, M I Rudina3

  • 1Novosibirsk Research Institute of Tuberculosis, Ministry of Health of the Russian Federation, Novosibirsk, Russia. YShSchwartz@mail.ru.

Bulletin of Experimental Biology and Medicine
|August 19, 2018
PubMed

Insights

Extracellular vesicles from apoptotic M1 macrophages boost nitric oxide (NO) production, while M2 vesicles have minimal impact. Macrophage exposure to these apoptotic microparticles induces endotoxic tolerance.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Macrophages play a crucial role in immune responses.
  • Apoptosis, or programmed cell death, releases extracellular vesicles.
  • Different macrophage phenotypes (M0, M1, M2) have distinct functions.

Purpose of the Study:

  • To investigate the impact of extracellular vesicles from apoptotic macrophages on nitric oxide (NO) production.
  • To determine if the phenotype of the 'donor' macrophage influences the effect of its apoptotic microparticles on recipient macrophages.
  • To explore the potential for apoptotic microparticles to induce endotoxic tolerance.

Main Methods:

  • Primary cultures of peritoneal macrophages (M0, M1, M2 phenotypes) were induced to undergo apoptosis.
  • Extracellular vesicular particles, including apoptotic bodies and microvesicles, were isolated.
  • Recipient macrophages were incubated with these microparticles.
  • Spontaneous and lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in recipient macrophages was measured.

Main Results:

  • Apoptotic microparticles from M1 macrophages significantly stimulated basal NO production.
  • Pre-incubation with M1 apoptotic bodies or microvesicles altered the LPS-induced NO response in recipient macrophages, with microvesicles suppressing NO production.
  • Apoptotic microparticles from M2 macrophages had minimal effect on basal NO production and did not enhance LPS-stimulated NO production.
  • Incubation with apoptotic microparticles from both M1 and M2 macrophages led to the formation of endotoxic tolerance.

Conclusions:

  • The phenotype of macrophages undergoing apoptosis dictates the immunomodulatory effects of their released extracellular vesicles.
  • M1-derived apoptotic microparticles can enhance basal NO production but may lead to suppressed or altered responses upon LPS stimulation.
  • Exposure to apoptotic microparticles from different macrophage phenotypes induces endotoxic tolerance, suggesting a mechanism for immune dampening.
Keywords:
apoptotic bodiesapoptotic microvesiclesmacrophagenitric oxide

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