The relative number of macrophages/microglia expressing macrophage colony-stimulating factor and its receptor decreases in multiple sclerosis lesions.
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.
Werner
Katrin
K
Department of Neuropathology, Charité, Humboldt-Universität, Campus Virchow-Klinikum, Berlin, Germany.
Bitsch
Andreas
A
Bunkowski
Stephanie
S
Hemmerlein
Bernhard
B
Brück
Wolfgang
W
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D002633:Chemotaxis / Q000235:genetics; D002648:Child; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor