MIP-1 alpha, MCP-1, GM-CSF, and TNF-alpha control the immune cell responsethat mediates rapid phagocytosis of myelin from the adult mouse spinal cord

The slow immune response in the adult mammalian CNS results in slow myelin phagocytosis along degenerating white matter after injury. This has importa nt consequences for axon regeneration because of the presence of axon growt h 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 molecula r switches that turn on this immune cell response. Using reverse transcript ion PCR analysis, we show that mRNA expression of macrophage inflammatory p rotein-1 alpha (MIP-1 alpha), macrophage chemotactic protein-1 (MCP-1), gra nulocyte macrophage-colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) in the spinal cord is rapidly and transiently upre gulated after intraspinal injection of LPC. Neutralizing these signaling mo lecules 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 regenerati on and demyelinating disease.