Monocyte chemoattractant protein-1 is a pathogenic component in a model for a he

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Mol Cell Neurosci. 2008 Feb;37(2):359-66.

Monocyte chemoattractant protein-1 is a pathogenic component in a

model for a hereditary peripheral neuropathy.

Fischer S, Kleinschnitz C, Müller M, Kobsar I, Ip CW, Rollins B,

i R.

Department of Neurology, Developmental Neurobiology, University of

Wuerzburg, Wuerzburg, Germany.

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.