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

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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. GLIA 40:121–129, 2002.
Funding Information
  • Gemeinnützige Hertie-Stiftung