More MS news articles for December 2000

Contact With CD200 Down-Regulates Macrophages and Brain Microglia

WESTPORT, CT (Reuters Health) Dec 01 - Mice lacking the CD200 gene have more numerous and activated macrophages, including resident microglia in the central nervous system, and are more susceptible to autoimmune disease. The findings are reported in the December 1st issue of Science.

"Our data suggest that CD200 delivers an inhibitory signal to cells within the broader myeloid lineage and particularly to macrophages," Dr. Jonathon D. Sedgwick, from the DNAX Research Institute of Molecular and Cellular Biology in Palo Alto, California, told Reuters Health. "As CD200 is expressed very broadly and constitutively, this would suggest that it is essential that macrophages are kept constantly in check by interactions of this type," he said.

To look at the role of the CD200 protein, Dr. Sedgwick and colleagues generated mice lacking the CD200 gene. The mice appeared normal, but myeloid cells were more numerous and macrophages were more activated.

Brain microglia were also more activated and formed aggregates associated with inflammation or neurodegeneration. The response of brain microglia after facial nerve transection was also dramatically accelerated, with maximal activation 4 days after surgery compared with 7 days for normal mice.

The researchers next looked at two mouse models of autoimmunity that involve macrophages. In experimental autoimmune encephalomyelitis, a model for multiple sclerosis, normal mice developed disease 10 days after peptide immunization, which was significantly accelerated by 3 days in mice lacking CD200. In collagen-induced arthritis, less than 10% of mice normally develop disease after peptide injection. However, over 50% of mice lacking CD200 developed arthritis as early as day 20 after immunization.

"The major finding of this work is the definition of a novel regulatory pathway for macrophages that is mediated by cell to cell contacts rather than via secreted factors," Dr. Sedgwick said. "That microglia, the resident macrophages of the brain, is also regulated by this mechanism is of interest given the expression of CD200 on neurons--thus, the implication that ongoing interactions between neurons and microglia are important for regulating microglial cell responses."

In the journal, the researchers suggest that their work "has important and broad implications for treatment of neurodegenerative diseases like Alzheimer's disease or for varied pathologies involving hyperactivation of the myeloid lineage." In the interview, Dr. Sedgwick said that the next step is to figure out how CD200 regulates the function of myeloid cells by studying signaling through the CD200 receptor.

Science 2000;290:1768-1771.

Copyright © 2000 Reuters Ltd.