PERIPHERAL-NERVE INJURY INDUCES SCHWANN-CELLS TO EXPRESS 2 MACROPHAGEPHENOTYPES - PHAGOCYTOSIS AND THE GALACTOSE-SPECIFIC LECTIN MAC-2

In N mice, peripheral nerve injury is followed by the normal rapid pro gression of Wallerian degeneration: Schwann cells proliferate and lose their myelin, which is phagocytized and metabolized by blood-borne ma crophages. The role of Schwann cells in myelin phagocytosis is debated . Additionally, the molecular mechanisms underlying myelin phagocytosi s by the two cell types are not well understood. To elucidate the role of Schwann cells as phagocytes we studied, electron microscopically, in vivo and in vitro degenerating, frozen, and neuroma nerve segments. The major cell types composing these tissues differed: Schwann and ma crophages in in vivo degenerating; Schwann in in vitro degenerating; m acrophages in frozen; Schwann, macrophages, and fibroblasts in neuroma nerve segments. Both macrophages and Schwann cells phagocytized myeli n. We further studied, by immunocytochemistry and immunoblot analysis, the expression of molecules that are characteristically displayed by inflammatory and mature murine macrophages: MAC-1 (the C3b complement receptor), MAC-2 (a galactose-specific lectin), the Fc receptor, and t he F4/80 antigen. All were detected in the macrophage-rich, in vivo de generating, frozen, and neuroma nerve segments. Surprisingly, MAC-2 wa s also expressed in the macrophage-scarce, Schwann-rich, in vitro dege nerating nerve. Immunocytochemistry and immunoblot analysis of isolate d non-neuronal cells revealed that both macrophages and Schwann cells displayed MAC-5 on their surface and in their cytoplasm. Morphometry u nveiled that galactose and lactose specifically inhibited myelin phago cytosis, as predicted if MAC-2 was mediating myelin phagocytosis by le ctinophagocytosis (lectin-mediated phagocytosis). The role of MAC-5 in mediating myelin phagocytosis was further supported by two observatio ns made in W mice that display very slow progression of Wallerian dege neration. First, the failure to degenerate in vivo was associated with deficient MAC-5 production. Second, degeneration that occurred in vit ro was associated with MAC-5 production. Furthermore, a strong positiv e correlation between levels of MAC-5 expression and the extent of mye lin destruction by phagocytosis was observed over a wide range of valu es.