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Expression of functional CD40 by vascular endothelial cells
D Hollenbaugh1, N Mischel-Petty, C P Edwards
1Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
The Journal of Experimental Medicine
|July 1, 1995
Summary
Vascular endothelial cells express CD40, a molecule that, when activated by T cells, promotes leukocyte adhesion during inflammation. This interaction is crucial for inflammatory responses and diseases.
Area of Science:
- Immunology
- Cell Biology
- Vascular Biology
Background:
- Activated T cells and vascular endothelium interactions are key in inflammation.
- Endothelial cell activation and T cell recruitment are critical processes in inflammatory responses.
Purpose of the Study:
- To investigate the expression and role of CD40 on vascular endothelial cells.
- To determine how CD40-ligand interactions influence endothelial cell activation and leukocyte adhesion.
Main Methods:
- Studied CD40 expression on endothelial cells using recombinant CD40 ligand (sgp39).
- Assessed leukocyte adhesion and expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1).
- Analyzed CD40 expression in healthy and inflamed human skin tissues.
Main Results:
- Endothelial cells express CD40, regulated by inflammatory agents.
- CD40-ligand interaction activates endothelial cells, promoting leukocyte adhesion partly via E-selectin.
- sgp39 upregulated intercellular adhesion molecule 1 and enhanced tumor necrosis factor alpha-induced vascular cell adhesion molecule 1 expression.
- CD40 expression was significantly higher in inflamed skin compared to healthy skin.
Conclusions:
- CD40-CD40 ligand interactions on vascular endothelium contribute to inflammatory responses.
- Upregulation of CD40 on endothelial cells in inflammation suggests a role in disease pathogenesis.
- Targeting CD40-mediated interactions could be a therapeutic strategy for inflammatory diseases.