Shape change of blood platelets induced by myelin basic protein

Laubscher, Andreas; Pletscher, A.; Honegger, C. G.; Richards, John; Colombo, Victor

doi:10.1007/bf01949954

Cited by 8 publications

(4 citation statements)

References 19 publications

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“…4D–E). These studies also revealed that MBP-induced platelet shape change is not inhibited by antagonists of 5-hydroxy-tryptamine receptors [40], [41], which is similar with the fact that antagonists and blockers of multiple channels failed to rescue MBP-induced neurotoxicity (Fig. 6E).…”

Section: Discussionsupporting

confidence: 73%

“…This idea can also be supported by other studies. Previous studies showed that the shape change of blood platelets induced by MBP can be attenuated by acidic mucopolysaccharide heparin [40], [41], which is similar with the protective effect of acidic phospholipids on MBP-induced neurotoxicity (Fig. 4D–E).…”

Section: Discussionsupporting

confidence: 72%

“…MBP has been well-studied as an antigen to activate immune response throughout the nervous system, which causes immune injury, such as in multiple sclerosis (MS) [1], [37]–[39]. Previous studies have also shown that soluble MBP changes the shape of platelets [40], [41], interrupts artificial membrane and acidic lipid vesicles [42], [43], stimulates proliferation of astrocytes and Schwann cells [44], [45] and depolarizes the neuronal membrane [46]. However, the effect of MBP on neurons is still largely unclear.…”

Section: Introductionmentioning

confidence: 99%

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Myelin Basic Protein Induces Neuron-Specific Toxicity by Directly Damaging the Neuronal Plasma Membrane

Zhang

Zheng

et al. 2014

PLoS ONE

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The central nervous system (CNS) insults may cause massive demyelination and lead to the release of myelin-associated proteins including its major component myelin basic protein (MBP). MBP is reported to induce glial activation but its effect on neurons is still little known. Here we found that MBP specifically bound to the extracellular surface of the neuronal plasma membrane and induced neurotoxicity in vitro. This effect of MBP on neurons was basicity-dependent because the binding was blocked by acidic lipids and competed by other basic proteins. Further studies revealed that MBP induced damage to neuronal membrane integrity and function by depolarizing the resting membrane potential, increasing the permeability to cations and other molecules, and decreasing the membrane fluidity. At last, artificial liposome vesicle assay showed that MBP directly disturbed acidic lipid bilayer and resulted in increased membrane permeability. These results revealed that MBP induces neurotoxicity through its direct interaction with acidic components on the extracellular surface of neuronal membrane, which may suggest a possible contribution of MBP to the pathogenesis in the CNS disorders with myelin damage.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Myelin Basic Protein Induces Neuron-Specific Toxicity by Directly Damaging the Neuronal Plasma Membrane

Zhang

Zheng

et al. 2014

PLoS ONE

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“…MBP is well known to be a nonspecific ligand forming weak contacts with many cellular proteins. This protein changes the shape of platelets,8 interrupts artificial membrane and acidic lipid vesicles,9,10 stimulates proliferation of astrocytes and Schwann cells,10–12 and depolarizes the neuronal membrane 13. Recent investigation has shown that MBP is a potent and specific ligand for the αMβ2-integrin (Mac 1, CD11b/CD18) 14.…”

Section: Introductionmentioning

confidence: 99%

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

Tsitsilashvili

Sepashvili

Chikviladze

et al. 2019

JIR

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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.

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Blood Platelets as Models for Neurons: Uses and Limitations

Pletscher

Laubscher

1980

Current Topics in Extrapyramidal Disorders

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Shape change of blood platelets induced by myelin basic protein

Cited by 8 publications

References 19 publications

Myelin Basic Protein Induces Neuron-Specific Toxicity by Directly Damaging the Neuronal Plasma Membrane

Myelin Basic Protein Induces Neuron-Specific Toxicity by Directly Damaging the Neuronal Plasma Membrane

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

Blood Platelets as Models for Neurons: Uses and Limitations

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