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Endothelial microparticles (EMP) bind and activate monocytes: elevated EMP-monocyte conjugates in multiple sclerosis.
Wenche Jy1, Alireza Minagar, Joaquin J Jimenez
1The Wallace H. Coulter Platelet Laboratory, Department of Medicine, University of Miami School of Medicine, Miami, FL 33136, USA. wjy@med.miami.edu
Frontiers in Bioscience : a Journal and Virtual Library
|September 9, 2004
Summary
Endothelial microparticles (EMP) form conjugates with monocytes, increasing inflammation and cell migration in multiple sclerosis (MS) during exacerbation. These EMP-monocyte conjugates (EMP-MoC) may serve as a key marker for MS disease activity.
Area of Science:
- Neuroimmunology
- Vascular Biology
- Cellular Biology
Background:
- Elevated plasma endothelial microparticles (EMP) are observed in multiple sclerosis (MS) during exacerbation.
- The precise role of EMP in MS pathogenesis, particularly in inflammatory cell trafficking, remains incompletely understood.
Purpose of the Study:
- To investigate the formation of EMP-monocyte conjugates (EMP-MoC) in MS.
- To determine the role of EMP-MoC in the transendothelial migration of inflammatory cells in MS.
- To assess EMP-MoC as a potential biomarker for MS disease activity.
Main Methods:
- Flow cytometry was used to quantify EMP-leukocyte conjugation, specifically EMP-monocyte conjugates (EMP-MoC), in MS patients during exacerbation and remission, and in controls.
- Adhesion molecules involved in EMP-MoC formation were identified using antibodies against CD54 and CD62E for EMP, and CD45 for leukocytes.
- In vitro assays assessed the effect of bound EMP on monocyte activation (CD11b expression) and their migratory capacity across a cerebral endothelial cell layer.
Main Results:
- EMP-MoC levels were significantly elevated in MS patients during exacerbation compared to remission and controls, correlating with Gadolinium-enhancing (GD+) MRI lesions.
- In vitro, EMP preferentially bound to monocytes, leading to increased CD11b expression and a 2.6-fold increase in transmigration across endothelial cells.
- Blockade of CD54 significantly reduced EMP binding to monocytes, indicating its crucial role in conjugate formation. CD54+ EMP were primarily bound to monocytes, while CD62E+ EMP were found both free and bound.
Conclusions:
- Phenotypic subsets of EMP interact differently with monocytes, with CD54 playing a key role in binding and activation.
- EMP-MoC formation enhances monocyte activation and transendothelial migration, potentially contributing to MS inflammation.
- Elevated EMP-MoC levels in MS exacerbation suggest they could serve as a sensitive biomarker for disease activity.