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 nervous system after transection of axons, leading to the recruitment of mononuclear cells from the systemic circulation. However, the exact mechanisms regulating this cell invasion have not yet been clarified in detail. Chemokines and their receptors play a central role in leukocyte trafficking, in particular the chemokine MCP-1 has been strongly implicated in macrophage recruitment to the injured nervous system. The present study investigates the course of Wallerian degeneration after transection of the sciatic nerve in mice 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 for three typical macrophage antigens (F4/80, Mac-1, LFA-1). The chemokine receptor CCR2 was expressed by infiltrating cells in the transected nerve stumps. Macrophage invasion was significantly impaired in CCR2-knockout mice when compared with wildtype controls and CCR5-deficient mice. Subsequently, there was a corresponding decrease in myelin phagocytosis due to the reduced invasion of phagocytic macrophages. These data demonstrate the involvement of the chemokine receptor CCR2 in macrophage recruitment to the injured nervous system.
Siebert
H
H
Department of Neuropathology, Charité, Humboldt-University, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
Sachse
A
A
Kuziel
W A
WA
Maeda
N
N
Brück
W
W
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D002465:Cell Movement / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D016177:Macrophage-1 Antigen / Q000032:analysis; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009185:Myelin Proteins / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D012584:Sciatic Nerve / Q000737:chemistry / Q000293:injuries* / Q000473:pathology; D014855:Wallerian Degeneration / Q000276:immunology* / Q000473:pathology
D000943:Antigens, Differentiation; C515335:Ccr2 protein, mouse; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D009185:Myelin Proteins; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; C036763:monocyte-macrophage differentiation antigen