The chemokine receptor CXCR2 is differentially regulated on glial cells in vivo but is not required for successful remyelination after cuprizone-induced demyelination

Glia. 2008 Aug 1;56(10):1104-13. doi: 10.1002/glia.20682.

Abstract

Unravelling the factors that can positively influence remyelination is one of the major challenges in multiple sclerosis research. Expression of the chemokine receptor CXCR2 on oligodendrocytes both in vitro and in MS lesions has suggested a possible role for CXCR2 in the recruitment of oligodendrocyte precursor cells (OPC). To investigate the function of CXCR2 during remyelination in vivo, we studied this receptor in cuprizone-induced demyelination and subsequent remyelination. We found that CXCR2 is constitutively expressed on OPC, whereas on macrophages/microglia CXCR2 is upregulated upon activation during demyelination. Hence, the expression of CXCR2 is differentially regulated in oligodendrocytes and macrophages/microglia. Furthermore, we subjected CXCR2-/- mice to the cuprizone model demonstrating that remyelination was not altered in comparison to wildtype controls. In addition, the number of OPC and the amount of microglial accumulation were similar in both CXCR2-/- and wildtype animals during the whole demyelination and remyelination process. These results suggest that despite expression on OPC and microglia CXCR2 plays only a minor role during remyelination.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cuprizone / toxicity*
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / metabolism*
  • Demyelinating Diseases / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Myelin Sheath / drug effects
  • Myelin Sheath / pathology
  • Myelin Sheath / physiology*
  • Neuroglia / drug effects
  • Neuroglia / metabolism*
  • Neuroglia / pathology
  • Neuroglia / physiology*
  • Receptors, Interleukin-8B / biosynthesis*
  • Receptors, Interleukin-8B / physiology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Stem Cells / physiology

Substances

  • Receptors, Interleukin-8B
  • Cuprizone