POLYMORPHONUCLEAR LEUKOCYTE-PLATELET INTERACTION - ROLE OF P-SELECTININ THROMBOXANE B-2 AND LEUKOTRIENE C-4 COOPERATIVE SYNTHESIS

In PMN/platelet suspensions stimulated by fMLP giant mixed aggregates are formed and TxB(2) and LTC(4) are synthesized as the result of the cooperation in the arachidonic acid (AA) metabolism during cell/cell c ontact. PMN-derived cathepsin G induced the expression of P-selectin o n platelet surface. GE12, an antibody against P-selectin: significantl y reduced mixed cell aggregates. GE12 did not affect platelet aggregat ion induced by PMN-derived supernatants, indicating that the inhibitor y effect of GE12 on mixed cell aggregation depends on inhibition of PM N/platelet adhesion. GE12 significantly reduced TxB(2) and LTC(4) prod uction in PMN/platelet mixed cell suspensions stimulated by fMLP. As p reviously reported, synthesis of H-3-TxB(2) in H-3-AA-labeled PMN/unla beled platelets indicates that platelets utilize H-3-AA from PMN. H-3- LTC(4) production in unlabeled PMN/H-3-AA-labeled platelets indicates that bidirectional routes are utilized in this system for LTC(4) synth esis. GE12 significantly reduced H-3-TxB(2) and H-3-LTC(4) synthesis. These results show that cathepsin G released by activated PMN induces the expression of P-selectin on platelet membrane: this adhesive glyco protein modulates cell-cell contact and transcellular metabolism of AA .