CYTOKINE-REGULATED EXPRESSION OF E-SELECTIN, INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1), AND VASCULAR CELL-ADHESION MOLECULE-1 (VCAM-1) IN HUMAN INTESTINAL MICROVASCULAR ENDOTHELIAL-CELLS

Endothelial cells (EC) recruit circulating leukocytes to sites of infl ammation, partly by expression of endothelial-leukocyte adhesion molec ules, Whereas the regulation of some adhesion molecules is well charac terized in cultured HUVEC, similar data for microvascular human test s ystems are limited, We studied the cytokine-regulated expression of va scular cell adhesion molecules E-selectin, vascular cell adhesion mole cule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in cul tured human intestinal microvascular endothelial cells (HIMEC), E-sele ctin and VCAM-1 were induced, and ICAM-1 was enhanced, in a dose-depen dent fashion after stimulation with IL-1 beta, TNF-alpha, and LPS, Eac h adhesion molecule displayed characteristic time-related responses co mparable to those obtained with HUVEC, and each molecule supported adh esion of leukocytes, Notable disparities between the two endothelial t est systems were that 1) expression of total cellular E-selectin (but not surface membrane expression) was sustained after 72 h of IL-1 beta stimulation in HIMEC, contrasting a rapid biphasic response in HUVEC; 2) LPS did not maintain prolonged expression of ICAM-1 and VCAM-1 in HIMEC; and 3) VCAM-1 protein was dose-dependently up-regulated by IL-4 in HUVEC, peaking after 8 h, while IL-4 had only a negligible effect on the expression of this protein in HIMEC, In conclusion, the regulat ion of these adhesion molecules appears to be somewhat different in HI MEC compared with HUVEC, and the differences from available data on sk in-derived microvascular endothelial cell cultures are to some extent substantial, Our findings document the importance of using relevant en dothelial cell culture systems for studies of leukocyte-endothelial ce ll interactions.