PMID- 18326085
OWN - NLM
STAT- MEDLINE
DCOM- 20080425
LR  - 20191110
IS  - 1044-7431 (Print)
IS  - 1044-7431 (Linking)
VI  - 37
IP  - 2
DP  - 2008 Feb
TI  - Monocyte chemoattractant protein-1 is a pathogenic component in a model for a 
      hereditary peripheral neuropathy.
PG  - 359-66
AB  - 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.
FAU - Fischer, Stefan
AU  - Fischer S
AD  - Department of Neurology, Developmental Neurobiology, University of Wuerzburg, 
      Wuerzburg, Germany.
FAU - Kleinschnitz, Christoph
AU  - Kleinschnitz C
FAU - Muller, Marcus
AU  - Muller M
FAU - Kobsar, Igor
AU  - Kobsar I
FAU - Ip, Chi Wang
AU  - Ip CW
FAU - Rollins, Barrett
AU  - Rollins B
FAU - Martini, Rudolf
AU  - Martini R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Myelin P0 Protein)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*genetics/immunology/metabolism
MH  - Chemokines/genetics/immunology/metabolism
MH  - Chemotaxis, Leukocyte/genetics
MH  - Disease Models, Animal
MH  - Macrophages/*immunology/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Myelin P0 Protein/genetics
MH  - Myelin Sheath/immunology/metabolism/pathology
MH  - Nerve Fibers, Myelinated/immunology/metabolism/pathology
MH  - Peripheral Nerves/*immunology/metabolism/physiopathology
MH  - Peripheral Nervous System Diseases/*genetics/*immunology/physiopathology
MH  - Polyradiculoneuropathy/genetics/immunology/physiopathology
MH  - Schwann Cells/*immunology/metabolism
EDAT- 2008/03/08 09:00
MHDA- 2008/04/26 09:00
CRDT- 2008/03/08 09:00
PHST- 2008/03/08 09:00 [pubmed]
PHST- 2008/04/26 09:00 [medline]
PHST- 2008/03/08 09:00 [entrez]
AID - 10.1016/j.mcn.2007.10.012 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2008 Feb;37(2):359-66. doi: 10.1016/j.mcn.2007.10.012.