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Updated: Jul 11, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Downregulation of macrophage inhibitory molecules in multiple sclerosis lesions
Nathalie Koning1, Lars Bö, Robert M Hoek
1Netherlands Institute for Neuroscience, Amsterdam, the Netherlands. n.koning@nin.knaw.nl
Objective:
Inflammatory and demyelinating activity of activated resident macrophages (microglia) and recruited blood-borne macrophages are considered crucial in multiple sclerosis (MS) lesion development. The membrane glycoproteins CD200 and CD47, highly expressed on neurons, are mediators of macrophage inhibition via their receptors CD200R and signal-regulatory protein alpha, respectively, on myeloid cells. We determined the expression pattern of immune inhibitory molecules in relation to genes involved in macrophage activation and MS lesion pathology.
Methods:
Laser dissection microscopy was combined with real-time polymerase chain reaction to quantitatively study these gene expression patterns in specific subareas (rim, center, and normal-appearing white matter) of chronic active and inactive MS lesions.
Results:
Hallmarks of MS pathology were confirmed by messenger RNA expression patterns of glial fibrillary acidic protein, neurofilament (NF), myelin basic protein, growth factors, chemokines and receptors, and macrophage activation markers, although expression of osteopontin and alphaB-crystallin was decreased. CD200 and CD47 were downregulated in the center of chronic active and inactive MS lesions. CD47 expression was also decreased in the rim of chronic active lesions, where complement expression was increased. This expression profile was also found in normal-appearing white matter surrounding these lesions, but not surrounding inactive lesions. Expression of CD200R and signal-regulatory protein alpha was not altered.
Interpretation:
These data suggest that diminished immune inhibition via decreased CD200 and CD47 expression contributes to a disturbed equilibrium in macrophage and microglia activation in MS lesions. Furthermore, this may result in a proinflammatory predisposition in the area surrounding chronic active lesions, thereby contributing to axonal injury, demyelination, and possible lesion expansion.
Insights
Decreased expression of immune inhibitory molecules CD200 and CD47 in multiple sclerosis (MS) lesions suggests reduced macrophage regulation. This may drive inflammation and damage around active MS lesions.
Area of Science:
- Neuroimmunology
- Multiple Sclerosis Pathogenesis
Background:
- Activated macrophages (microglia and blood-borne) are key in multiple sclerosis (MS) lesion development.
- Neuronal glycoproteins CD200 and CD47 normally inhibit macrophage activity via their receptors.
Purpose of the Study:
- To investigate the expression of immune inhibitory molecules (CD200, CD47) in relation to MS lesion pathology.
- To determine how these molecules correlate with macrophage activation markers in different MS lesion areas.
Main Methods:
- Quantitative gene expression analysis using laser dissection microscopy and real-time PCR.
- Examination of specific regions: lesion rim, center, and normal-appearing white matter in chronic active and inactive MS lesions.
Main Results:
- CD200 and CD47 were downregulated in MS lesion centers and CD47 in active lesion rims.
- Normal-appearing white matter near active lesions showed similar expression changes, unlike that near inactive lesions.
- While some MS hallmarks were confirmed, osteopontin and alphaB-crystallin expression decreased; CD200R and signal-regulatory protein alpha expression remained unchanged.
Conclusions:
- Reduced CD200 and CD47 expression in MS lesions may impair immune inhibition, disrupting macrophage/microglia balance.
- This imbalance could promote a pro-inflammatory state around active lesions, contributing to axonal injury, demyelination, and lesion expansion.
