PMID- 11425892 OWN - NLM STAT- MEDLINE DCOM- 20010726 LR - 20220309 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 21 IP - 13 DP - 2001 Jul 1 TI - 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. PG - 4649-56 AB - 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. FAU - Ousman, S S AU - Ousman SS AD - Centre for Research in Neuroscience, Montreal General Hospital Research Institute and McGill University, Montreal, Quebec, Canada, H3G 1A4. FAU - David, S AU - David S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Antibodies) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL3) RN - 0 (Chemokine CCL4) RN - 0 (Cytokines) RN - 0 (Lysophosphatidylcholines) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Antibodies/administration & dosage MH - Chemokine CCL2/antagonists & inhibitors/genetics/metabolism MH - Chemokine CCL3 MH - Chemokine CCL4 MH - Cytokines/antagonists & inhibitors/genetics/*metabolism MH - Demyelinating Autoimmune Diseases, CNS/chemically induced/*immunology/pathology MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors/genetics/metabolism MH - Lysophosphatidylcholines/pharmacology MH - Macrophage Activation/drug effects/immunology MH - Macrophage Inflammatory Proteins/antagonists & inhibitors/genetics/metabolism MH - Macrophages/immunology/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Microinjections MH - Myelin Sheath/drug effects/*immunology MH - Neutrophil Infiltration/drug effects/immunology MH - Neutrophils/immunology MH - Phagocytosis/immunology MH - RNA, Messenger/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Spinal Cord/drug effects/*immunology/*metabolism/pathology MH - Spinal Cord Diseases/chemically induced/*immunology/pathology MH - T-Lymphocytes/immunology MH - Tumor Necrosis Factor-alpha/antagonists & inhibitors/genetics/metabolism PMC - PMC6762369 EDAT- 2001/06/27 10:00 MHDA- 2001/07/28 10:01 PMCR- 2002/01/01 CRDT- 2001/06/27 10:00 PHST- 2001/06/27 10:00 [pubmed] PHST- 2001/07/28 10:01 [medline] PHST- 2001/06/27 10:00 [entrez] PHST- 2002/01/01 00:00 [pmc-release] AID - 21/13/4649 [pii] AID - 5351 [pii] AID - 10.1523/JNEUROSCI.21-13-04649.2001 [doi] PST - ppublish SO - J Neurosci. 2001 Jul 1;21(13):4649-56. doi: 10.1523/JNEUROSCI.21-13-04649.2001.