Two phases of macrophages: Inducing maturation and death of oligodendrocytes in vitro co-culture

Abstract

Background: The plasticity of macrophages in the immune response is a dynamic situation dependent on external stimuli. The activation of macrophages both has beneficial and detrimental effects on mature oligodendrocytes (OLs) and myelin. The activation towards inflammatory macrophages has a critical role in the immune-mediated oligodendrocytes death in multiple sclerosis (MS) lesions.

New method: We established an in vitro co-culture method to study the function of macrophages in the survival and maturation of OLs.

Results: We revealed that M1 macrophages decreased the number of mature OLs and phagocytosed the myelin. Interestingly, non-activated as well as M2 macrophages contributed to an increase in the number of mature OLs in our in vitro co-culture platform.

Comparison with existing methods: We added an antibody against an OL surface antigen in our in vitro co-cultures. The antibody presents the OLs to the macrophages enabling the investigation of direct interactions between macrophages and OLs.

Conclusion: Our co-culture system is a feasible method for the investigation of the direct cell-to-cell interactions between OLs and macrophages. We utilized it to show that M2 and non-activated macrophages may be employed to enhance remyelination.

Keywords: Multiple sclerosis; Oligodendrocytes; Peritoneal macrophages; Remyelination.