Essential role of ICAM-1 in mediating monocyte adhesion to aortic endothelial cells.
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.
Kevil
C G
CG
Department of Genomics and Pathobiology, University of Alabama at Birmingham, 35294-0019, USA.
Patel
R P
RP
Bullard
D C
DC
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology* / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1