INDUCIBLE NITRIC-OXIDE AND PROSTACYCLIN PRODUCTIONS ARE DIFFERENTLY CONTROLLED BY EXTRACELLULAR-MATRIX AND CELL-DENSITY IN HUMAN VASCULAR ENDOTHELIAL-CELLS

Both cell-matrix and cell-cell interactions are important regulators o f the function of most human cells. In this study we investigated how these interactions controlled the production of vasodilators nitric ox ide (NO), and prostacyclin (PGI(2)), in freshly isolated human umbilic al vein endothelial cells (HUVECs). On the reconstituted extracellular matrix (ECM) Matrigel freshly isolated HUVECs treated with interleuki n-1 beta, lipopolysaccharide, and interferon-gamma, produced more NO, but less PGI(2), than on gelatin substratum. High cell density was ess ential for inducibility of NO production in cells plated on gelatin su bstratum, but not on ECM. In cells plated on gelatin substratum at low cell density, which mimicked conventional HUVEC culturing conditions, both inducible NO production and the inducible NO synthase (iNOS) mRN A levels, detected by competitive RT-PCR, were low. However, inducible PGI(2) production remained high in these cells. Highest inducible NO productions were observed in HUVECs that presumably had best maintaine d their original differentiated phenotype. Thus our data imply that th e inducible NO and PGI(2) productions of freshly isolated HUVECs were differently controlled by the extracellular matrix and cell density. O ur data suggest that both cell-matrix and cell-cell interactions may h ave a strong influence on the proinflammatory cytokine responses of hu man vascular endothelial cells. (C) 1997 Wiley-Liss, Inc.