Related Experiment Videos
VCAM-1-positive microglia target oligodendrocytes at the border of multiple sclerosis lesions
John W Peterson1, Lars Bö, Sverre Mörk
1Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.
Abstract:
The distribution and lineage of vascular cell adhesion molecule-1 (VCAM-1)-positive cells was investigated in 43 lesions from the brain tissue of patients with multiple sclerosis (MS). Numerous VCAM-1-positive macrophages/microglia were detected at the edges of MS lesions. Quantitative analysis of 6 active, 7 chronic active, and 4 chronic inactive MS lesions identified most VCAM-1-positive cells at the actively demyelinating borders of active (102/mm3) and chronic active (29/mm3) lesions, but rarely in chronic inactive lesions (4/mm3). Further, approximately 17% of the VCAM-1-positive cells closely apposed or surrounded oligodendrocyte perikarya at the edges of active and chronic active lesions that were sites of ongoing demyelination. Endothelial cells were VCAM-1-negative in both lesion and non-lesion MS brain tissue. This report is the first to document direct microglial interaction with oligodendrocytes in MS.
Insights
Vascular cell adhesion molecule-1 (VCAM-1) positive macrophages/microglia cluster at active multiple sclerosis (MS) lesion borders, interacting with myelin-producing cells. This study reveals direct microglial contact with oligodendrocytes during MS demyelination.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Neuropathology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
- The role of specific cell adhesion molecules and immune cell interactions in MS lesion pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the distribution and lineage of vascular cell adhesion molecule-1 (VCAM-1)-positive cells in multiple sclerosis (MS) brain lesions.
- To determine the spatial relationship between VCAM-1-positive cells and oligodendrocytes in active MS lesions.
Main Methods:
- Immunohistochemical analysis of VCAM-1 expression in brain tissue from 43 MS patients.
- Quantitative assessment of VCAM-1-positive cells in active, chronic active, and chronic inactive MS lesions.
- Microscopic examination of cell-cell interactions at lesion borders.
Main Results:
- Numerous VCAM-1-positive macrophages/microglia were found at the actively demyelinating borders of active and chronic active MS lesions.
- VCAM-1-positive cells were rarely detected in chronic inactive lesions.
- Approximately 17% of VCAM-1-positive cells were closely associated with or surrounding oligodendrocyte perikarya in active lesions.
Conclusions:
- VCAM-1 expression is prominent on macrophages/microglia at active MS lesion sites.
- These VCAM-1-positive myeloid cells engage directly with oligodendrocytes in areas of active demyelination.
- This study provides the first evidence of direct microglial interaction with oligodendrocytes in the context of multiple sclerosis.