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In vitro intercellular adhesion molecule-1 expression on brain endothelial cells in multiple sclerosis
N Tsukada1, M Matsuda, K Miyagi
1Department of Health Medical Center and Neurology, Shinshu University, Matsumoto, Japan.
Insights
T lymphocytes from multiple sclerosis (MS) patients, particularly during exacerbations, increase intercellular adhesion molecule-1 (ICAM-1) expression on brain endothelial cells. This suggests ICAM-1
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Intercellular adhesion molecule-1 (ICAM-1) plays a role in immune cell trafficking.
- The expression and origin of ICAM-1 on brain endothelial cells in multiple sclerosis (MS) are not fully understood.
Purpose of the Study:
- To investigate the origin and expression of ICAM-1 on human brain endothelial cells.
- To determine the role of T cells from MS patients in ICAM-1 expression.
Main Methods:
- In vitro study using human brain endothelial cells and T cells from MS patients.
- Histochemical techniques and flow cytometry to analyze ICAM-1 expression.
- Enzyme-linked immunosorbent assay (ELISA) to quantify soluble ICAM-1.
Main Results:
- Flow cytometry revealed significantly increased ICAM-1-positive cells after incubating brain endothelial cells with T cells from MS patients during exacerbation (P < 0.01).
- ELISA showed higher soluble ICAM-1 levels in supernatants from mixtures of brain endothelial cells and lymphocytes from patients with acute relapsing MS during exacerbation and chronic progressive MS compared to controls (P < 0.001 and P < 0.01, respectively).
Conclusions:
- Lymphocytes from MS patients, especially during acute relapses, induce increased ICAM-1 expression on brain endothelial cells.
- These findings support the involvement of ICAM-1 in the pathogenesis of multiple sclerosis.
Abstract:
To investigate the origin of intercellular adhesion molecule-1 (ICAM-1) and its expression on brain endothelial cells, we studied the expression in vitro of ICAM-1 on human brain endothelial cells after incubation of T cells from patients with multiple sclerosis (MS) using a histochemical technique and flow cytometry. We determined soluble forms of ICAM-1 (ICAM-1) in the supernatants after mixtures of brain endothelial cells and T cells from patients with MS using an enzyme-liked immunosorbent assay. Flow cytometric analysis showed that a number of ICAM-1-positive cells were significantly increased after incubation of brain endothelial cells with T cells from patients with acute relapsing MS during an exacerbation as compared with those of controls (P < 0.01). Patients with acute relapsing MS during an exacerbation and chronic progressive MS exhibited higher levels of ICAM-1 in the supernatants of mixtures with brain endothelial cells and lymphocytes than those of controls (P < 0.001 and P < 0.01, respectively). These results suggest that lymphocytes from patients with acute relapsing MS during an exacerbation lead to an increased expression of ICAM-1 on the brain endothelial cells and add to evidence involving this adhesion molecule in the pathogenesis of MS.
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