THROMBIN RECEPTOR-ACTIVATING PEPTIDES DIFFERENTIALLY STIMULATE PLATELET-DERIVED GROWTH-FACTOR PRODUCTION, MONOCYTIC CELL-ADHESION, AND E-SELECTIN EXPRESSION IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

Recent studies have shown that the synthetic peptides SFL LRN and SFL LRN PND KYEPF (thrombin receptor-activating peptides (TRAP)) derived f rom the deduced sequence of the new amino terminus of the cleaved thro mbin receptor can mimic thrombin receptor activation, act as full agon ists for platelet activation, and induce prostaglandin I-2 production as well as cytosolic Ca2+ increase in human umbilical vein endothelial cells (HUVEC). Here, we have compared the ability of these synthetic peptide ligands and thrombin to stimulate platelet-derived growth fact or (PDGF) production by, and monocyte adhesion to, HUVEC. Thrombin (50 units/ ml) and TRAP (25 mu M) maximally stimulated monocyte adhesion. Furthermore, the stimulation of E-selectin cell surface expression an d the steady-state E-selectin mRNA levels by thrombin and TRAP were co mparable. Thrombin (50 units/ml) stimulated PDGF production 400% above the basal level in 24 h, whereas the 6-mer and 14-mer TRAP, even at 2 00 mu M, did not significantly stimulate PDGF production. Northern ana lysis, however, revealed that TRAP at 100 mu M stimulated PDGF-A and - B chain mRNA expression to a level similar to that induced by thrombin . These results suggest that activation of cell signaling by TRAP can mimic thrombin and is sufficient for the stimulation of monocyte adhes ion to HUVEC; however, thrombin-stimulated PDGF production by HUVEC ma y require mechanisms in addition to the signaling events initiated by TRAP or may require the participation of a novel thrombin receptor.