title: Origin of pathogenic macrophages and endoneurial fibroblast-like cells in an animal model of inherited neuropathy.
abstract: Macrophages have recently been shown to be critically involved in the pathogenesis of genetically determined demyelination in mice heterozygously deficient for P0 (P0(+-)). Since little is known about the origin of these cells, we created chimeric P0(+-) mice by transplanting bone marrow from green fluorescent protein (GFP)-transgenic mice into irradiated P0(+-) mice. When analyzing chimeric P0(+-) mice, we could determine two populations (GFP(+) and GFP(-)) of endoneurial macrophages that became phagocytic for myelin and increased in number. We found that both GFP(-) resident macrophages and GFP(+) macrophages proliferated in peripheral nerves of P0(+-) mice but not in nerves of chimeric or nonchimeric P0(++) mice. These findings demonstrate a so far poorly recognized role of resident endoneurial macrophages in demyelinating neuropathies. Surprisingly, we also found GFP(+) cells that unequivocally showed the morphological characteristics of fibroblasts. These blood-borne fibroblast-like cells express the common hematopoetic stem cell marker CD34 and might comprise another cell type of potential importance for immune regulation in hereditary demyelinating neuropathies.
authors.affiliation: Department of Neurology, Bayerische Julius-Maximilians-Universität Würzburg, D-97080 Würzburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Mäurer
authors.forename: Marcus
authors.initials: M
authors.lastname: Müller
authors.forename: Igor
authors.initials: I
authors.lastname: Kobsar
authors.forename: Christine
authors.initials: C
authors.lastname: Leonhard
authors.forename: Rudolf
authors.initials: R
authors.lastname: Martini
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kiefer
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000276:immunology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D009186:Myelin Sheath / Q000473:pathology; D010525:Peripheral Nerves / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000473:pathology*; D010587:Phagocytosis / Q000276:immunology; D010641:Phenotype; D013126:Spinal Nerve Roots / Q000473:pathology / Q000648:ultrastructure; D018183:Transplantation Chimera
chemical_list: D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins