The chemokine receptor CCR2 is involved in macrophage recruitment to the injured peripheral nervous system

Wallerian degeneration is one of the most elementary reactions of the nervo us system after transection of axons, leading to the recruitment of mononuc lear cells from the systemic circulation. However, the exact mechanisms reg ulating this cell invasion have not yet been clarified in detail. Chemokine s and their receptors play a central role in leukocyte trafficking, in part icular the chemokine MCP-1 has been strongly implicated in macrophage recru itment to the injured nervous system. The present study investigates the co urse of Wallerian degeneration after transection of the sciatic nerve in mi ce deficient in two chemokine receptors: CCR2, the main receptor for MCP-1, and CCR5, a marker for Th1 T lymphocytes but also present on macrophages. The number of invading macrophages was determined by immunocytochemistry fo r three typical macrophage antigens (F4/80, Mac-1, LFA-1). The chemokine re ceptor CCR2 was expressed by infiltrating cells in the transected nerve stu mps. Macrophage invasion was significantly impaired in CCR2-knockout mice w hen compared with wildtype controls and CCR5-deficient mice. Subsequently, there was a corresponding decrease in myelin phagocytosis due to the reduce d invasion of phagocytic macrophages. These data demonstrate the involvemen t of the chemokine receptor CCR2 in macrophage recruitment to the injured n ervous system. (C) 2000 Elsevier Science B.V. All rights reserved.