RT Journal Article SR Electronic T1 Macrophages Are Eliminated from the Injured Peripheral Nerve via Local Apoptosis and Circulation to Regional Lymph Nodes and the Spleen JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 3401 OP 3408 DO 10.1523/JNEUROSCI.21-10-03401.2001 VO 21 IS 10 A1 Tanja Kuhlmann A1 Andreas Bitsch A1 Christine Stadelmann A1 Heike Siebert A1 Wolfgang Brück YR 2001 UL http://www.jneurosci.org/content/21/10/3401.abstract AB 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 degeneration was induced in adult male C57Bl/6 mice by transecting the right sciatic nerve. Five days after transection, the male sciatic nerves were transplanted into female recipient mice by placing them exactly parallel to the host sciatic nerves. Nerves of the female recipient mice were also transected to induce breakdown of the blood–nerve barrier in the host animal. Apoptosis was assessed by morphological, immunohistochemical (activated caspase-3), and molecular (DNA fragmentation) methods in transplanted, recipient, and in control nerves. A subpopulation of macrophages within the degenerating nerves died locally by apoptosis in each experiment. The fate of the male macrophages within the transplanted nerves and the host organism was investigated by in situ hybridization with a Y-chromosome-specific DNA probe (145SC5). In situhybridization specifically stained cells within the transplanted male nerve. Y-chromosome-positive cells were detected not only inside the transplanted nerve, but also inside the female host nerve, the perineurial tissue, the local perineurial blood vessels, draining lymph nodes and the spleen of the female host, suggesting hematogenous as well as lymphatic 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.