Macrophages are eliminated from the injured peripheral nerve via local apoptosis and circulation to regional lymph nodes and the spleen

The present study investigated the fate of macrophages in peripheral nerves undergoing Wallerian degeneration, especially their disappearance from the injured nerves after phagocytosis of axonal and myelin debris. Wallerian d egeneration was induced in adult male C57Bl/6 mice by transecting the right sciatic nerve. Five days after transection, the male sciatic nerves were t ransplanted into female recipient mice by placing them exactly parallel to the host sciatic nerves. Nerves of the female recipient mice were also tran sected to induce breakdown of the blood-nerve barrier in the host animal. A poptosis was assessed by morphological, immunohistochemical (activated casp ase-3), and molecular (DNA fragmentation) methods in transplanted, recipien t, and in control nerves. A subpopulation of macrophages within the degener ating nerves died locally by apoptosis in each experiment. The fate of the male macrophages within the transplanted nerves and the host organism was i nvestigated by in situ hybridization with a Y-chromosome-specific DNA probe (145SC5). In situ hybridization specifically stained cells within the tran splanted male nerve. Y-chromosome-positive cells were detected not only ins ide the transplanted nerve, but also inside the female host nerve, the peri neurial tissue, the local perineurial blood vessels, draining lymph nodes a nd the spleen of the female host, suggesting hematogenous as well as lympha tic elimination of macrophages from the injured nerve. These data indicate that local apoptosis and systemic elimination via circulation to the local lymph nodes and the spleen are involved in the disappearance of macrophages from the injured peripheral nervous system.