AN INHIBITORY EFFECT OF CAMONAGREL - A NEW THROMBOXANE SYNTHASE INHIBITOR, ON P-SELECTIN-MEDIATED PLATELET PMN ADHESION/

P-selectin (PADGEM protein, GMP-140 or CD 62) is a glycoprotein of pla telet or-granules and endothelial Weibel-Palade bodies that, by mediat ing cellular adhesion, initiates recruitment of leukocytes and lymphoc ytes into injured tissue. Both of the endothelial antiplatelet autacoi ds prostacyclin (PGI(2)) and nitric oxide (NO) have been demonstrated to inhibit P-selectin expression, Prostaglandin endoperoxides PGG(2)/P GH(2), that are generated by activated platelets have been demonstrate d to be used by endothelium for generation of prostacyclin, In an expe rimental model in vitro that resembles vessel wall/platelet/PMN intera ction in vivo, we found that aspirin (100 mu M), a COX inhibitor, but not L-NMMA (100 mu M) and a NO-synthase inhibitor, reversed the inhibi tory effect of arterial wall on P-selectin mediated platelet/PMN adhes ion, The anti-adhesive potency of vessel wall reversed by aspirin was dose-dependently restored by camonagrel (3-100 mu M), a new TXA(2) syn thase inhibitor, We conclude that selective TXA(2)-synthase inhibitors may inhibit P-selectin mediated platelet/PMN adhesion by augmenting f ormation of prostacyclin by vessel walls.