SYNTHESIS AND RELEASE OF PLATELET-ACTIVATING-FACTOR AND EICOSANOIDS IN HUMAN ENDOTHELIAL-CELLS INDUCED BY DIFFERENT AGONISTS

Production of platelet-activating factor (PAF) and eicosanoids by huma n umbilical vein endothelial cells (HUVEC) after stimulation with diff erent agonists has been studied. Significant amounts of PAF were measu red in the cellular fraction after treatment with thrombin (2 NIHu/ml) , calcium ionophore A23187 (2 muM) and histamine (100 muM) (110.3 +/- 14.3, 80.7 +/- 19.2 and 119.2 +/- 22.4 pg/10(5) cells, respectively). Only thrombin caused a partial release of PAF into the supernatant. IL -1alpha (0.1 nM), TNF (1 nM), arachidonic acid (10 muM) and endothelin (0.1 muM) were not able to induce any PAF synthesis. High levels of 6 -keto-PGF1alpha were found after stimulation with thrombin and calcium ionophore A23187 (8641 +/- 2575 and 6715 +/- 3340 pg/10(5) cells, res pectively). Cytokines IL-1alpha and TNF were also able to stimulate PG I2 synthesis, although to a lesser extent. PGE2 production increased a fter treatment with thrombin and calcium ionophore A23187 three- and t wo-fold, respectively. Our results confirm that stimulated HUVEC are a ble to synthesize PAF and eicosanoids simultaneously, the relative amo unts depending upon the agonist used. None of the agonists studied sho wed any significant effect on 15-HETE production.