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Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
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Myelin basic protein charge isomers change macrophage polarization

Elene Tsitsilashvili1, Maia Sepashvili1,2, Marika Chikviladze1

  • 1Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia, lali_shanshiashvili@iliauni.edu.ge.

Journal of Inflammation Research
|February 19, 2019
PubMed

Insights

Myelin basic protein (MBP) isomers differentially regulate macrophage polarization. The C1 isomer promotes M2 macrophage phenotypes, while the C8 isomer drives M1 polarization, impacting immune responses after neuronal injury.

Area of Science:

  • Neuroimmunology
  • Cellular Biology

Background:

  • Neuronal injury triggers immune cell infiltration and myelin breakdown.
  • Myelin basic protein (MBP) acts as a ligand for immune cells, with post-translational modifications creating various isomers.
  • The distinct effects of MBP isomers on macrophage activity remain largely unknown.

Purpose of the Study:

  • To investigate the differential effects of MBP charge isomers on macrophage polarization.
  • To determine how specific MBP isomers influence macrophage phenotypes (M1 vs. M2).

Main Methods:

  • Purified MBP isomers were used to treat RAW 264.7 macrophages.
  • Macrophage polarization markers (iNOS for M1, Arginase-1 for M2) were quantified via ELISA.
  • Rac activity was assessed using a G-LISA assay.
  • Receptor for advanced glycation end-products (RAGE) and high mobility group box 1 (HMGB1) expression were analyzed by Western blot.

Main Results:

  • The C1 isomer of MBP increased arginase-1 (M2 marker) and Rac activity, while decreasing iNOS (M1 marker) and not affecting HMGB1.
  • The C1 isomer significantly elevated surface RAGE expression.
  • The deiminated C8 isomer of MBP increased HMGB1 secretion but did not alter arginase-1 or RAGE levels.

Conclusions:

  • MBP isomers exhibit distinct immunomodulatory functions.
  • The C1 isomer promotes M2 macrophage polarization, potentially via RAGE and Rac signaling.
  • The C8 isomer appears to induce an M1-like phenotype, evidenced by HMGB1 secretion.
Abstract

Keywords:
Arginase-1HMGB1RAGEiNOS

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