Ousman & David (2001): Myelin loss in adult spinal cord and the role of immune cells

[Wise Young]

• Ousman SS and David S (2001). MIP-1alpha, MCP-1, GM-CSF, and TNF-alpha control the immune cell response that mediates rapid phagocytosis of myelin from the adult mouse spinal cord. J Neurosci. 21 (13): 4649-56. Summary: The slow immune response in the adult mammalian CNS results in slow myelin phagocytosis along degenerating white matter after injury. This has important consequences for axon regeneration because of the presence of axon growth inhibitors in myelin. In addition, abnormal immune cell responses in the CNS lead to demyelinating disease. Lysophosphatidylcholine (LPC) can induce an inflammatory response in the CNS, producing rapid demyelination without much damage to adjacent cells. In this study, we searched for the molecular switches that turn on this immune cell response. Using reverse transcription PCR analysis, we show that mRNA expression of macrophage inflammatory protein-1alpha (MIP-1alpha), macrophage chemotactic protein-1 (MCP-1), granulocyte macrophage-colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) in the spinal cord is rapidly and transiently upregulated after intraspinal injection of LPC. Neutralizing these signaling molecules with function-blocking antibodies suppresses recruitment of T-cells, neutrophils, and monocytes into the spinal cord, as well as significantly reduces the number of phagocytic macrophages and the demyelination induced by LPC. These findings will have important implications for CNS regeneration and demyelinating disease. <http://www.ncbi.nlm.nih.gov/htbin-po...r&uid=11425892
http://www.jneurosci.org/cgi/content/full/21/13/4649
http://www.jneurosci.org/cgi/content...ct/21/13/4649> Centre for Research in Neuroscience, Montreal General Hospital Research Institute and McGill University, Montreal, Quebec, Canada, H3G 1A4.

[This message was edited by Wise Young on September 23, 2001 at 09:34 PM.]