Rapid response of identified resident endoneurial macrophages to nerve injury

Macrophages play a central role in the pathogenesis of peripheral neuropath y but the role of resident endoneurial macrophages is undefined because no discriminating markers exist to distinguish them from infiltrating hematoge nous; macrophages. We identified and characterized resident endoneurial mac rophages during Wallerian degeneration in radiation bone marrow chimeric ra ts created by transplanting wild-type Lewis rat bone marrow into irradiated TK-tsa transgenic Lewis rats. In such animals, resident cells carry the tr ansgene, whereas hematogenous cells do not. As early as 2 days after sciati c nerve crush and before the influx of hematogenous macrophages, resident t ransgene-positive endoneurial macrophages underwent morphological and immun ophenotypic signs of activation. At the same time, resident macrophages pha gocytosing myelin were found, and proliferation was detected by bromodeoxyu ridine incorporation. Continuous bromodeoxyuridine feeding revealed that re sident endoneurial macrophages sequentially retracted their processes, prol iferated, and expressed the ED1 antigen, rendering them morphologically ind istinguishable from hematogenous macrophages. Resident endoneurial macropha ges thus play an early and active role in the cellular events after nerve l esion before hematogenous macrophages, enter the nerve. They may thus be cr itically involved in the pathogenesis of peripheral neuropathy particularly at early stages of the disease and may act as sensors of pathology much li ke their central nervous system counterparts, the microglial cells.