cxcr2 signaling protects oligodendrocytes and restricts demyelination in a mouse model of viral-induced demyelinationcxcr2信号保护少突胶质细胞和小鼠模型的限制脱髓鞘viral-induced脱髓鞘.pdfVIP

CXCR2 Signaling Protects Oligodendrocytes and Restricts Demyelination in a Mouse Model of Viral-Induced Demyelination 1 1 4 1,2,3 Martin P. Hosking , Emanuele Tirotta , Richard M. Ransohoff , Thomas E. Lane * 1 Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, United States of America, 2 Institute for Immunology, University of California Irvine, Irvine, California, United States of America, 3 Sue and Bill Gross Stem Cell Center, University of California Irvine, Irvine, California, United States of America, 4 Neuroinflammation Research Center, Department of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America Abstract Background: The functional role of ELR-positive CXC chemokines during viral – induced demyelination was assessed. Inoculation of the neuroattenuated JHM strain of mouse hepatitis virus (JHMV) into the CNS of susceptible mice results in an acute encephalomyelitis that evolves into a chronic demyelinating disease, modeling white matter pathology observed in the human demyelinating disease Multiple Sclerosis. Methodology/Principal Findings: JHMV infection induced the rapid and sustained expression of transcripts specific for the ELR (+) chemokine ligands CXCL1 and CXCL2, as well as their binding receptor CXCR2, which was enriched within the spinal cord during chronic infection. Inhibiting CXCR2 signaling with neutralizing antiserum significantly (p,0.03) delayed clinical recovery. Moreover, CXCR2 neutralization was associated with an increase in the severity of demyelination that was independent of viral recrudescence or modulation of neuroinflammation. Rather, blocking CXCR2 was assoc