MACROPHAGE RECRUITMENT IN DIFFERENT MODELS OF NERVE INJURY - LYSOZYMEAS A MARKER FOR ACTIVE PHAGOCYTOSIS

Macrophages play critical roles in both degenerative and regenerative processes following peripheral nerve injury, These include phagocytosi s of debris, stimulation of Schwann cell dedifferentiation and prolife ration, and salvage of myelin lipids for reutilization during regenera tion, To better define the role of macrophages, we studied models of p rimary demyelination (tellurium intoxication) and secondary demyelinat ion (nerve crush and cut), Sections of paraformaldehyde-fixed rat scia tic nerves at various stages of demyelination were stained with monocl onal antibody ED1, a standard macrophage marker, and a polyclonal anti serum specific for lysozyme (LYS), Near the peak of demyelination in a ll three models, LYS immunoreactivity colocalized with ED1 staining. M acrophages present in nerve after the period of maximal phagocytosis o f myelin were much less immunoreactive for LYS, These results suggest LYS is a good marker for macrophages which are active in phagocytosis. Tellurium intoxication, which causes synchronous demyelination and su bsequent remyelination of only about 25% of myelin internodes, recruit ed more macrophages (and induced more lysozyme expression) than either nerve crush or cut, which cause demyelination of all internodes dista l to the injury site, This suggests that Schwann cells may recruit mac rophages soon after metabolic insult and prior to actual demyelination , The final signal for macrophage recruitment is not directly related to the amount of damaged myelin. In the models listed above, steady st ate mRNA levels for apolipoprotein E (ApoE; possible mediator of chole sterol salvage), LYS, and P-o (major structural protein of PNS myelin) , were analyzed by Northern blot analysis, LYS mRNA levels peaked shar ply in all models, with a temporal pattern consistent with the expecte d presence of activated, phagocytic macrophages. The temporal pattern for ApoE mRNA levels differed in the 3 models, but ApoE expression was consistent with its proposed role in salvage of cholesterol during re myelination. (C) 1995 Wiley-Liss, Inc.