Cytokine activation of human macro- and microvessel-derived endothelial cells.

The effects of the inflammatory cytokines, tumor necrosis factor (TNF alpha), interleukin-1 alpha (IL-1), and gamma interferon (IFN gamma) on macro- and microvessel-derived endothelial cell proteolytic, adhesion protein and prostaglandin synthetic activities were compared. TNF alpha treatment of human umbilical vein endothelial (HUVE) cells induced urokinase-type plasminogen (uPA) activity, increased HUVE uPA-dependent extracellular matrix (ECM) degradation, and accelerated matrix remodeling and endothelial differentiation into tubes or cord-like structures. All of the aforementioned effects of TNF alpha on HUVE uPA-dependent activities were abrogated by co- or pretreatment with IFN gamma. In contrast, endothelium derived from human lung (HLE) exhibited high constitutive uPA and uPA-dependent matrix degradation and rapid tube formation in Matrigel, activities all unaffected by TNF alpha or IFN gamma. Endothelium derived from human rheumatoid synovium (HSE) exhibited uPA-dependent activities intermediate between the HLE and HUVE. TNF alpha or IL-1 treatment of HUVE potently induced surface ICAM-1 expression, whereas these cytokines were relatively ineffective on HLE and HSE ICAM-1 expression. Co-incubation with IFN gamma synergistically elevated TNF alpha or IL-1 induced ICAM-1 expression in HUVE, HLE, and HSE. The major prostaglandin synthesized by HUVE was PGI2, in contrast to HLE and HSE which produced PGE2 as the major product. Although cytokine treatment increased prostanoid production in all three cell types, HLE were not responsive to IL-1, and HSE demonstrated the greatest increase in prostaglandin synthetic capacity. These studies underline important differences not only in the "constitutive" activities expressed by EC from different vascular beds, but also in the responsiveness to proinflammatory cytokines alone or in combination. These observations further emphasize the need to study the endothelial cell derived from the vascular bed of interest rather than extrapolate from results obtained with HUVE or other macrovessel-derived endothelium.