title: Interactions between Schwann cells and macrophages in injury and inherited demyelinating disease.
abstract: In this article we first discuss the factors that regulate macrophage recruitment, activation, and myelin phagocytosis during Wallerian degeneration and some of the factors involved in the termination of inflammation at the end of the period of Wallerian degeneration after peripheral nerve injuries. In particular, we deal with the early events that trigger chemokine and cytokine expression; the role of phospholipase A(2) in initiating the breakdown of compact myelin, and chemokine, cytokine expression; and the role of MCP-1, MIP-1alpha, and IL-1beta in macrophage recruitment and myelin phagocytosis. We also discuss how inflammation may be switched off and the recently identified role of the Nogo receptor on activated macrophages in the clearance of these cells from the injured nerve. In the second half of the article we focus on the role of certain Schwann cell borne cytokines and chemokines, such as M-CSF and MCP-1 as well as intracellular signaling that regulate their expression in animal models of inherited demyelinating disease. Additionally, we present the preservation of sensory nerves fibers from macrophage attack in these animal models as a challenging paradigm for the development of putative treatment approaches. Finally, we also discuss the similarities and differences in these Schwann cell-macrophage responses in injury-induced Wallerian degeneration and inherited demyelinating diseases. Knowledge of the molecular mechanisms underlying Schwann cell-macrophage interaction under pathological conditions is an important prerequisite to develop effective treatment strategies for various peripheral nerve disorders.
authors.affiliation: Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Straβe 11, Wuerzburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Martini
authors.affiliation: Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Straβe 11, Wuerzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischer
authors.affiliation: Center for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Canada.
authors.forename: Rubèn
authors.initials: R
authors.lastname: López-Vales
authors.affiliation: Center for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: David
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology*; D011129:Polyradiculoneuropathy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D012583:Schwann Cells / Q000166:cytology / Q000276:immunology*; D014855:Wallerian Degeneration / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D018925:Chemokines; D016207:Cytokines