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Essential role of ICAM-1 in mediating monocyte adhesion to aortic endothelial cells
C G Kevil1, R P Patel, D C Bullard
1Department of Genomics and Pathobiology, University of Alabama at Birmingham, 35294-0019, USA.
Insights
Intercellular adhesion molecule-1 (ICAM-1) is crucial for monocyte adhesion to endothelial cells in vascular diseases. Genetic studies show ICAM-1 deficiency completely inhibits monocyte binding, highlighting its critical role.
Area of Science:
- Vascular Biology
- Immunology
- Cellular Adhesion
Background:
- Monocyte-endothelial cell interactions are key in vascular diseases like atherosclerosis.
- Intercellular adhesion molecule-1 (ICAM-1) is a suspected mediator of monocyte adhesion, but its precise role is debated.
Purpose of the Study:
- To genetically determine the contribution of ICAM-1 in mediating monocyte adhesion to mouse aortic endothelial cells (MAEC).
Main Methods:
- Utilized a genetic approach comparing wild-type and ICAM-1 knockout (ICAM-1(-/-)) MAEC.
- Assessed monocyte adhesion following stimulation with oxidized low-density lipoprotein and tumor necrosis factor-alpha.
Main Results:
- Oxidized low-density lipoprotein significantly increased monocyte adhesion to wild-type MAEC.
- ICAM-1(-/-) MAEC showed complete inhibition of monocyte binding when treated with oxidized low-density lipoprotein.
- Tumor necrosis factor-alpha also induced monocyte adhesion to wild-type MAEC, with significant binding only at higher doses in ICAM-1(-/-) MAEC.
Conclusions:
- ICAM-1 plays a critical role in mediating monocyte-endothelial cell interactions.
- These interactions are vital in response to stimuli involved in inflammatory vascular diseases.
Abstract:
Monocyte-endothelial cell interactions have been implicated in the pathogenesis of a number of vascular diseases that target arterial and aortic endothelium, including atherosclerosis. Many different adhesion molecules, such as intercellular adhesion molecule (ICAM)-1, are thought to mediate monocyte binding to endothelial cells during the development of these diseases. However, conflicting results have been reported regarding the specific role of ICAM-1 in these events. In this study, we used a genetic approach to determine the contribution of ICAM-1 in mediating monocyte adhesion to mouse aortic endothelial cells (MAEC) derived from both wild-type and ICAM-1(-/-) mice. Treatment of wild-type MAEC with oxidized low-density lipoprotein significantly induced both WEHI 274.1 and whole blood monocyte adhesion, whereas similarly treated ICAM-1(-/-) MAEC showed a complete inhibition of monocyte binding. Dose-response treatment with tumor necrosis factor-alpha also increased monocyte adhesion to wild-type MAEC, but significant adhesion was only observed at higher doses for ICAM-1(-/-) MAEC. These data demonstrate a crucial role for ICAM-1-mediated monocyte-endothelial cell interactions in response to specific stimuli involved in inflammatory vascular diseases.