Macrophage responses and myelin clearance during Wallerian degeneration: relevance to immune-mediated demyelination

Macrophages are important effector cells in immune-mediated demyelination. Current concepts regarding their entry and activation focus on the effects of T-cell-derived cytokines. This presentation describes the responses of macrophages and microglia to a non-inflammatory, non-immune injury, Wallerian degeneration. During Wallerian degeneration in the peripheral nervous system (PNS), macrophages are promptly and abundantly recruited from the circulation, and myelin clearance is prompt. In the central nervous system (CNS), the appearance of macrophages is markedly slower, and entry from the circulation is modest or absent. Myelin clearance is similarly delayed. The nature of the factors promoting macrophage entry and activation in Wallerian degeneration, and the bases for the differences between PNS and CNS, are relevant to current issues in immune-mediated demyelination.