Macrophage colony stimulating factor is a crucial factor for the intrinsic macrophage response in mice heterozygously deficient for the myelin protein P0
| Autor: | Igor Kobsar, Martin Berghoff, Reinhard Kiefer, Rudolf Martini, Marcus Müller |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Macrophage colony-stimulating factor
Heterozygote Phagocytosis Green Fluorescent Proteins Population Polyradiculoneuropathy Biology Green fluorescent protein Mice Myelin Microscopy Electron Transmission Developmental Neuroscience medicine Animals Macrophage Peripheral Nerves education Myelin Sheath Bone Marrow Transplantation Cell Proliferation Mice Knockout Transplantation Chimera education.field_of_study Macrophage Colony-Stimulating Factor Macrophages Up-Regulation Cell biology Transplantation Chemotaxis Leukocyte Disease Models Animal medicine.anatomical_structure Neurology Immunology Endoneurium Hereditary Sensory and Motor Neuropathy Myelin P0 Protein |
| Zdroj: | Experimental Neurology. 203:55-62 |
| ISSN: | 0014-4886 |
| Popis: | Mouse mutants heterozygously deficient for the myelin protein P0 (P0+/-) resemble certain forms of human hereditary neuropathies. Endoneurial macrophages of intrinsic origin are intimately involved in the pathogenesis of the demyelinating neuropathy in these mutants. We have previously shown that deficiency for macrophage colony stimulating factor (M-CSF) prevents an increase of the number of endoneurial macrophages and alleviates the mutants' demyelinating phenotype. The aim of this study was to investigate which population of endoneurial macrophages - long-term resident macrophages or recently infiltrated macrophages - is affected by M-CSF deficiency. For this purpose, we generated bone marrow chimeric mice by transplanting GFP+ bone marrow into P0 mutants (P0+/-) and P0 mutants that lack M-CSF (P0+/- mcsf-op). This enabled us to discriminate recently infiltrated short-term resident GFP+ macrophages from long-term resident GFP- macrophages. Three months after bone marrow transplantation, P0+/- mice expressing M-CSF showed a substantial upregulation and activation of both GFP- and GFP+ macrophages in femoral nerves when compared to P0+/+ mice. In contrast, in P0+/- mcsf-op mutants, both GFP- and GFP+ macrophages did not substantially increase. Only small numbers of GFP+ but no GFP- macrophages were activated and phagocytosed myelin in chimeric P0+/- mcsf-op mutants, possibly reflecting recent activation outside the endoneurium before entering the nerve. Our findings demonstrate that M-CSF is crucial for the activation, in situ increase and myelin phagocytosis of both long-term and short-term resident endoneurial macrophages in P0+/- myelin mutants. M-CSF is, therefore, considered as a target candidate for therapeutic strategies to treat human demyelinating neuropathies. |
| Databáze: | OpenAIRE |
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