Differential effects of chemokines on oligodendrocyte precursor proliferation and myelin formation in vitro.
Chemokines have recently been postulated to have important functions in the central nervous system (CNS) in addition to their principal role of directional migration of leukocytes. In particular, it has been shown that chemokines may play a role in the regulation of oligodendrocyte biology. Here, we have chosen to study the role of certain chemokines in regulating myelination. We have used the murine oligodendrocyte precursor-like cell line, Oli-neu, and primary mixed cortical cultures as experimental systems to assess their activities on oligodendrocyte precursor proliferation and developmental in vitro myelination. GRO-alpha, IL-8, SDF-1alpha and RANTES dose-dependently increased proliferation of this mouse A2B5 precursor-like cell line, while MCP-1 did not. Furthermore, the CXC chemokines GRO-alpha, IL-8 and SDF-1alpha stimulated myelin basic protein synthesis in a dose-dependent manner in primary myelinating cultures and enhanced myelin segment formation in this system, while the CC chemokines MCP-1 and RANTES did not. We also demonstrate that the receptor for SDF-1alpha, CXCR4, is expressed in mixed cortical cultures by PDGFalphaR positive oligodendrocyte precursors (OLPs) as well as by Oli-neu cells. SDF-1alpha induced proliferation in primary mixed cultures and the Oli-neu cell line was mediated through this receptor. We propose, therefore, that CXC chemokines and in particular SDF-1alpha regulates CNS myelination via their effects on cells of the oligodendrocyte lineage, specifically stimulation of OLP proliferation.
Department of Immunology, Serono Pharmaceutical Research Institute 14, Chemin des Aulx, 1228 Plan les Ouates, Geneva, Switzerland.
Linda
L
Kadi
Ram
R
Selvaraju
Patricia
P
de Lys
Amanda E I
AE
Proudfoot
Timothy N C
TN
Wells
Ursula
U
Boschert
D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018925:Chemokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects*; D011509:Proteoglycans / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D018925:Chemokines; D005904:Glial Fibrillary Acidic Protein; D007334:Insulin-Like Growth Factor I; D019394:Ki-67 Antigen; D039841:Leukocyte L1 Antigen Complex; D008869:Microtubule-Associated Proteins; D004676:Myelin Basic Protein; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D019718:Receptors, CXCR4; D050825:Synaptosomal-Associated Protein 25; D000099216:Chondroitin Sulfate Proteoglycan 4; C079240:Mtap2 protein, mouse