Monocyte chemoattractant protein-1 is a pathogenic component in a model for a hereditary peripheral neuropathy.

Abstract

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.

• Authors: Stefan Fischer, Christoph Kleinschnitz, Marcus Müller, Igor Kobsar, Chi Wang Ip, Barrett Rollins, Rudolf Martini
• Journal: Molecular and cellular neurosciences (Mol Cell Neurosci) Vol. 37 Issue 2 Pg. 359-66 (Feb 2008) ISSN: 1044-7431 [Print] United States
• PMID: 18326085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ccl2 protein, mouse
• Chemokine CCL2
• Chemokines
• Myelin P0 Protein

Topics

• Animals
• Chemokine CCL2 (genetics, immunology, metabolism)
• Chemokines (genetics, immunology, metabolism)
• Chemotaxis, Leukocyte (genetics)
• Disease Models, Animal
• Macrophages (immunology, metabolism)
• Mice
• Mice, Knockout
• Mice, Transgenic
• Myelin P0 Protein (genetics)
• Myelin Sheath (immunology, metabolism, pathology)
• Nerve Fibers, Myelinated (immunology, metabolism, pathology)
• Peripheral Nerves (immunology, metabolism, physiopathology)
• Peripheral Nervous System Diseases (genetics, immunology, physiopathology)
• Polyradiculoneuropathy (genetics, immunology, physiopathology)
• Schwann Cells (immunology, metabolism)