REGULATION OF ADHESION MOLECULE EXPRESSION BY HUMAN SYNOVIAL MICROVASCULAR ENDOTHELIAL-CELLS IN-VITRO

Objective. To examine the in vitro expression of E-selectin, P-selecti n, intercellular adhesion molecule 1 (ICAM-1), ICAM-2, vascular cell a dhesion molecule 1 (VCAM-1), and platelet-endothelial cell adhesion mo lecule 1 (PECAM-1) by synovial microvascular endothelial cells (SMEC) in comparison with microvascular neonatal foreskin endothelial cells ( FSE) and macrovascular human umbilical vein endothelial cells (HUVE). Methods. Cultured endothelial cells were treated for 4 hours with medi um alone or tumor necrosis factor alpha (TNF alpha). The expression of endothelial adhesion molecules was evaluated by how cytometry, cell e nzyme-linked immunosorbent assay, and Northern blot analysis. Results. SMEC continuously expressed E-selectin under basal culture conditions , whereas FSE and HUVE did not, TNF alpha treatment of rheumatoid arth ritis (RA) SMEC resulted in sustained peak expression of E-selectin fo r up to 24 hours, which subsequently declined but remained elevated ev en at 72 hours. In contrast, peak E-selectin expression in FSE and HUV E occurred between 4 hours and 16 hours after TNF alpha treatment and then declined to near basal levels by 24-48 hours. SMEC expressed sign ificantly higher levels of ICAM-1 compared with HUVE under basal cultu re conditions. There was no difference between SMEC, FSE, and HUVE in the expression of P-selectin, VCAM-1, ICAM-2, or PECAM-1. Northern blo t analysis demonstrated that the levels of E-selectin expression by TN F alpha-stimulated endothelial cells correlated with their respective messenger RNA levels. Conclusion. Regulation of E-selectin and ICAM-1 expression in RA synovial endothelium is different from that in neonat al foreskin and human umbilical vein endothelium. The augmented expres sion of adhesion molecules in RA synovial endothelium may facilitate t he recruitment of leukocytes to this site.