<p>Myelin basic protein charge isomers change macrophage polarization</p>

Abstract

PurposeDuring a neuronal injury, a variety of immune cells infiltrate into the local microenvironment at the demyelination site. After the destruction of the intact myelin sheath, its major constituent myelin basic protein (MBP) dissociates from the plasma membrane and acts as a free ligand on the infiltrated immune cells. MBP exhibits charge microheterogeneity as a result of post-translational modifications, but the effect of various isomers of MBP on the activity of macrophages is not known.Materials and methodsMBP was isolated and purified from bovine brain white matter. RAW 264.7 macrophages were cultured in DMEM supplemented with heat-inactivated fetal bovine serum. For evaluation of macrophage polarization following treatment of RAW 264.7 cells with MBP charge isomers, inducible nitric oxide synthase (iNOS) expression (M1 phenotype marker) and arginase-1 expression (M2 phenotype marker) were determined in cell lysates by ELISA. To assess Rac activity, G-LISA Rac Activation Assay system was used. The expression of receptor for advanced glycation end-products (RAGE) and high mobility group box 1 (HMGB1) protein were assayed by Western blot analysis.ResultsOur results have shown that minimally modified C1 component of MBP increases the expression of arginase-1 in cells, decreases the expression of iNOS, does not change the secretion of HMGB1 protein, but significantly elevates surface expression of RAGE, and in parallel, increases the activity of small GTPase Rac. On the other hand, highly modified deiminated isomer C8-MBP increases the secretion of HMGB1 protein but does not change the expression of arginase-1 or the content of RAGE.ConclusionThese data indicate that deiminated C8 isomer of MBP tends to polarize RAW macrophages into M1 phenotypes, whereas C1 enhances the activity of M2 phenotype markers.

M2 Phenotype Macrophages Colocalize with Schwann Cells in Human Dental Pulp

“…Moreover, how Schwann cells modulate the macrophage phenotype remains largely unexplored (Stratton and Shah 2016). Myelin is an intrinsic Schwann cell component, and MBP, a major protein of the myelin sheath, has increased the expression of M2 markers (Tsitsilashvili et al 2019). MBP was devoid in Schwann cells of the subodontoblast layer, which supported a previous report (Couve et al 2018), and most cultured Schwann cells were devoid of MBP.…”

Nanoscale Bioreceptor Layers Comprising Carboxylated Polythiophene for Organic Electrochemical Transistor-Based Biosensors

“…After the binding of MBP, the surface zeta potential change is again not significant compared to the uncertainty of the measurement. Despite the positive charge of the MBP, , the dipolar orientation of the MBP, antibody, and counterions could result in a compensating negative potential at the interface. Also, because the 100 nm tracer particle used contains anionic sulfate groups on the surface, they could be sufficiently attracted to the MBP coatings to simply bind to them and thereby neutralize some of the positive charges brought by the MBP.…”

Citrullinated isomer of myelin basic protein can induce inflammatory responses in astrocytes

“…In addition, C8 is characterized by higher immunogenicity than C1 ( Tranquill et al, 2000 ). Interestingly the deiminated C8 isomer of MBP tends to polarize RAW macrophages into M1 phenotypes, whereas C1 enhances the activity of M2 phenotype markers ( Tsitsilashvili et al, 2019 ).…”