CXCR2-positive neutrophils are essential for cuprizone-induced demyelination: relevance to multiple sclerosis
| Autor: | Thomas E. Lane, Richard M. Ransohoff, Karen Choi, Anne C. Cotleur, Abdelmadjid Belkadi, Robert H. Miller, Dolly Ann Padovani-Claudio, Tao He, Caitlin Drescher, Lindsey Darnall, Taofang Hu, LiPing Liu |
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| Rok vydání: | 2010 |
| Předmět: |
Monoamine Oxidase Inhibitors
Multiple Sclerosis Neutrophils Mice Transgenic Biology Corpus callosum Receptors Interleukin-8B Article Corpus Callosum Pathogenesis Cuprizone Mice medicine Animals RNA Messenger CXC chemokine receptors Remyelination Demyelinating Disorder Receptor Myelin Sheath Mice Knockout Chimera General Neuroscience Multiple sclerosis medicine.disease Oligodendrocyte Mice Inbred C57BL Disease Models Animal Oligodendroglia medicine.anatomical_structure Immunology Neuroscience Myelin Proteins Demyelinating Diseases |
| Zdroj: | Nature Neuroscience |
| ISSN: | 1546-1726 1097-6256 |
| DOI: | 10.1038/nn.2491 |
| Popis: | Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Recent studies suggest diverse mechanisms underlying demyelination, including a subset of lesions involving interplay between metabolic insult to oligodendrocytes and inflammatory mediators. For mice of susceptible strains, cuprizone feeding results in oligodendrocyte cell loss and demyelination of the corpus callosum. Remyelination ensues, and has been extensively studied. Cuprizone-induced demyelination remains incompletely characterized. Here we show that mice lacking type 2 CXC chemokine receptor (CXCR2) are relatively resistant to cuprizone-induced demyelination, and CXCR2+ neutrophils from the circulation play an essential role in cuprizone-induced demyelination. Findings support a novel two-hit process of cuprizone-induced demyelination, mirroring proposals about pathogenesis of MS lesions featuring extensive oligodendrocyte cell loss. These data indicate that cuprizone-induced demyelination will provide a useful model for certain aspects of MS pathogenesis. |
| Databáze: | OpenAIRE |
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