Monocyte chemoattractant protein-1 is a pathogenic component in a model for a hereditary peripheral neuropathy
| Autor: | Rudolf Martini, Igor Kobsar, Christoph Kleinschnitz, Chi Wang Ip, Stefan Fischer, Marcus Müller, Barrett J. Rollins |
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| Rok vydání: | 2008 |
| Předmět: |
CCR2
Chemokine Polyradiculoneuropathy Schwann cell Mice Transgenic Nerve Fibers Myelinated Pathogenesis Cellular and Molecular Neuroscience Myelin Mice medicine Macrophage Animals Peripheral Nerves Molecular Biology Chemokine CCL2 Myelin Sheath Mice Knockout biology Myelin protein zero Monocyte Macrophages Peripheral Nervous System Diseases Cell Biology Chemotaxis Leukocyte Disease Models Animal medicine.anatomical_structure Immunology biology.protein Schwann Cells Chemokines Myelin P0 Protein |
| Zdroj: | Molecular and cellular neurosciences. 37(2) |
| ISSN: | 1044-7431 |
| Popis: | Macrophages are critically involved in the pathogenesis of genetically caused demyelination, as it occurs in models for inherited demyelinating neuropathies. It is presently unknown which factors link the Schwann cell-based myelin mutation to the activation of endoneurial macrophages. Here we identified the chemokine monocyte chemoattractant protein-1 (MCP-1) as a first and crucial factor upregulated in Schwann cells of mice heterozygously deficient for the myelin protein zero. The chemokine could be identified as an important mediator of macrophage immigration into peripheral nerves. Furthermore, a 50% reduction of chemokine expression by crossbreeding with MCP-1-deficient mice reduced the increase in macrophage numbers in the mutant nerves and lead to a robust amelioration of pathology. Surprisingly, the complete absence of MCP-1 aggravated the disease. Our findings show that reducing but not eliminating chemokine expression can rescue genetically caused demyelination that may be an interesting target in treating demyelinating diseases of the peripheral nervous system. |
| Databáze: | OpenAIRE |
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