The relative number of macrophages/microglia expressing macrophage colony-stimulating factor and its receptor decreases in multiple sclerosis lesions

Glia. 2002 Oct;40(1):121-9. doi: 10.1002/glia.10120.

Abstract

The activation of macrophages/microglia in multiple sclerosis (MS) lesions plays a central role in the effector phase of myelin breakdown. The precise patterns of macrophage/microglia activation during demyelination have not yet been defined. The growth and activating factor macrophage-colony stimulating factor (M-CSF) and its specific receptor (M-CSFR) may be involved in this process. The present study investigated the expression of M-CSF and M-CSFR mRNA by in situ hybridization in 60 lesions from 32 MS patients. In the control and periplaque white matter, microglia was almost completely M-CSFR positive. Irrespective of the demyelinating activity, an increased number of cells expressed M-CSF or M-CSFR mRNA within the lesions. However, despite the tremendous increase in macrophages/microglia within the lesions, the relative number of these cells expressing M-CSF or M-CSFR decreased. There was no correlation of M-CSF or M-CSFR expression with active myelin breakdown. The correlation between the clinical course and the expression of M-CSF or M-CSFR mRNA revealed significant differences with the lowest expression in primary progressive MS. These results suggest a downregulation of M-CSF and M-CSFR inside the MS plaque probably due to the high amount of macrophage-derived cytokines or mediators. Nevertheless, the differences in the relative number of cells expressing the M-CSF/M-CSFR pathway implicate that this pathway may be an important contributory factor in different forms of MS pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • Cell Count
  • Chemotaxis / genetics
  • Child
  • Disease Progression
  • Female
  • Gene Expression Regulation / genetics
  • Humans
  • Immunohistochemistry
  • Macrophage Colony-Stimulating Factor / genetics*
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Male
  • Microglia / cytology
  • Microglia / metabolism*
  • Middle Aged
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology
  • RNA, Messenger / metabolism
  • Receptor, Macrophage Colony-Stimulating Factor / genetics*
  • Up-Regulation / genetics

Substances

  • RNA, Messenger
  • Macrophage Colony-Stimulating Factor
  • Receptor, Macrophage Colony-Stimulating Factor