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Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis
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Pro-inflammatory polarization of macrophages is associated with reduced endoplasmic reticulum-mitochondria

Leandro Henrique de Paula Assis1, Gabriel de Gabriel Dorighello2, Helena Coutinho Franco de Oliveira1

  • 1Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, SP, 13083-872, Brazil.

Biochemical and Biophysical Research Communications
|March 27, 2022
PubMed

Insights

Pro-inflammatory stimuli alter macrophage metabolism and redox state, while anti-inflammatory signals enhance mitochondrial function. Endoplasmic reticulum-mitochondria interactions reveal distinct macrophage profiles.

Area of Science:

  • Immunology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • Macrophages are key immune cells involved in host defense, tissue remodeling, and inflammation.
  • Distinct inflammatory stimuli induce specific macrophage phenotypes and functional responses.
  • Understanding the interplay between macrophage phenotype, metabolism, and organelle interactions is crucial.

Purpose of the Study:

  • To investigate the relationship between macrophage immune phenotype and mitochondrial bioenergetics.
  • To examine the impact of inflammatory stimuli on cell redox state and ER-mitochondria interactions.
  • To elucidate how different stimuli modulate macrophage metabolic and redox profiles.

Main Methods:

  • Utilized THP-1 macrophages stimulated with pro-inflammatory (LPS + IFNγ) and anti-inflammatory (IL4 + IL13) agents.
  • Assessed mitochondrial bioenergetics using oxygen consumption rate measurements.
  • Analyzed cell redox state, oxidant production (superoxide, H2O2), and gene expression (NOX2, SOD1, MFN1/2, DRP1, FIS1).
  • Quantified endoplasmic reticulum (ER)-mitochondria contact sites via IP3R1-VDAC1 interaction measurements.

Main Results:

  • Pro-inflammatory stimuli (LPS + IFNγ) decreased oxidative metabolism and increased glycolysis.
  • Anti-inflammatory stimuli (IL4 + IL13) enhanced oxygen consumption and ATP production.
  • Stimuli differentially affected superoxide and hydrogen peroxide levels, with extra-mitochondrial oxidant sources identified.
  • LPS + IFNγ decreased ER-mitochondria contacts and upregulated mitochondrial dynamics genes, while IL4 + IL13 had no effect on ER-mitochondria interactions.

Conclusions:

  • Macrophage immune phenotype is intrinsically linked to mitochondrial bioenergetics and redox state.
  • Endoplasmic reticulum-mitochondria interaction patterns serve as a novel characteristic of macrophage immunological, metabolic, and redox profiles.
  • Specific inflammatory stimuli induce distinct metabolic and organelle interaction signatures in macrophages.
Keywords:
Endoplasmic reticulum-mitochondria interactionMacrophageMitochondrial respirationOxidants production

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