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Brain microvascular endothelial cells and leukocytes derived from patients with multiple sclerosis exhibit increased
J Lou1, M Chofflon, C Juillard
1Department of Anaesthesiology, Pharmacology, and Surgical Intensive Care, Hôpital Cantonal Universitaire, Centre Médical Universitaire (CMU), University of Geneva, Switzerland.
Abstract:
The adhesion properties of brain microvascular endothelial cells (MVEC) and leukocytes derived from patients with multiple sclerosis (MS) were investigated. Leukocytes and brain MVEC from MS patients exhibited significantly higher adhesion capacity than the same cells isolated from normal donors. Flow cytometry showed that MS-derived brain MVEC constitutively expressed higher levels of ICAM-1 and contained an increased proportion of MHC class II positive cells than normal brain MVEC. In contrast, no difference was seen for vascular cell adhesion molecule-1 and endothelial cell leukocyte adhesion molecule-1. Circulating leukocytes from MS patients expressed higher levels of LFA-1, a ligand of intercellular adhesion molecule-1 (ICAM-1), than did normal leukocytes. The data presented here suggest that the ICAM-1/LFA-1 interaction may determine cytoadherence of leukocytes to brain MVEC in MS.
Insights
Leukocytes and brain endothelial cells from multiple sclerosis (MS) patients show increased adhesion. The intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) interaction is implicated in MS leukocyte adhesion.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Vascular Biology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Leukocyte adhesion to brain microvascular endothelial cells (MVEC) is a critical step in immune cell infiltration into the brain.
Purpose of the Study:
- To investigate the adhesion properties of MVEC and leukocytes from MS patients.
- To identify molecular mechanisms contributing to leukocyte adhesion in MS.
Main Methods:
- Flow cytometry was used to analyze cell adhesion molecules on MVEC and leukocytes.
- Comparison of cells isolated from MS patients and healthy donors.
Main Results:
- MS-derived MVEC and leukocytes exhibited significantly higher adhesion capacity compared to normal controls.
- MS-derived MVEC showed increased expression of ICAM-1 and MHC class II.
- MS-derived leukocytes expressed higher levels of LFA-1.
Conclusions:
- The ICAM-1/LFA-1 pathway is a key mediator of leukocyte adhesion to brain MVEC in MS.
- These findings highlight potential therapeutic targets for reducing neuroinflammation in MS.