A role for myelin-derived components in the polarization of the macrophage phenotype

Abstract

MS is a chronic, inflammatory disease of the CNS, characterized by demyelination. Macrophages play an essential role in MS pathogenesis, as they contribute directly to CNS damage by secretion of pro-inflammatory and toxic mediators. Recent data however suggests an anti-inflammatory role for macrophages in MS after phagocytosis of myelin. It has not been established which myelin particles are capable of altering the macrophage phenotype. We hypothesize that internalization of myelin-derived components by macrophages leads to neuroprotection by these macrophages. To evaluate this hypothesis we will determine the phenotype as well as the immunomodulatory functions of macrophages laden with different myelin fractions. Furthermore, the effect of phagocytosis of myelin lipids on the phenotype and function of macrophages will be evaluated. We demonstrated that the size of the myelin particles has an effect on the phenotype of macrophages. Furthermore, phagocytosis of myelin leads to presentat