| Description |
The Glu-Leu-Arg (ELR)(+) chemokine C-X-C ligand 1 (CXCL1) is widely known to be involved in the recruitment of neutrophils to sites of inflammation by binding to the receptor C-X-C receptor 2 (CXCR2) expressed on the surface of neutrophils. The role of neutrophils in central nervous system (CNS) diseases has not been well characterized. Thus, we wanted to better understand the role of the CXCL1/CXCR2 signaling axis in the context of mouse models of the human demyelinating disease multiple sclerosis (MS), including infection with the JHM strain of mouse hepatitis virus (JHMV) and the myelin oligodendrocyte glycoprotein (MOG) peptide from amino acid 35 to 55 (MOG35-55)-induced Experimental Autoimmune Encephalomyelitis (EAE) model. In both models, the doxycycline (Dox)-inducible expression of CXCL1 from astrocytes selectively increased the recruitment of neutrophils into the spinal cord, correlating with an increase in both morbidity and demyelination. Antibody-mediated depletion of neutrophils during the overexpression of CXCL1 in the CNS correlated with a decrease in the severity of demyelination, indicating a role for neutrophils in white matter disease in JHMV-infected mice and MOG35-55-induced EAE. During CNS development, proliferation and migration of oligodendrocyte progenitor cells (OPCs) was dependent upon surface expression of the chemokine receptor CXCR2; genetic ablation of Cxcr2 resulted in misalignments in oligodendrocyte lineage cells (OLCs), decreased white matter in the spinal cord, and decreased myelin sheath thickness. Subsequent studies have determined that CXCR2 signaling has important roles on both hematopoietic and non-hematopoietic cells in remyelination in different models of demyelination. To better determine the role the CXCR2 signaling on OLCs during the pathogenesis of JHMV and MOG35-55 EAE, mice were engineered in which CXCR2 expression was inducibly ablated on oligodendroglia upon treatment with tamoxifen. Using both the JHMV infection and EAE models, we observed no significant changes in clinical disease, demyelination, or leukocyte infiltration into the CNS following tamoxifen-induced ablation in oligodendrocytes, indicating that CXCR2 in OLCs does not appear to be important in the pathogenesis of JHMV and MOG35-55 EAE. |
