Polymorphonuclear Leukocyte-Platelet Interaction: Role of P-Selectin in Thromboxane B₂ and Leukotriene C₄ Cooperative Synthesis

Summary

In PMN/platelet suspensions stimulated by fMLP giant mixed aggregates are formed and TxB₂ and LTC₄ are synthesized as the result of the cooperation in the arachidonic acid (AA) metabolism during cell/cell contact. PMN-derived cathepsin G induced the expression of P-selectin on platelet surface. GE12, an antibody against P-selectin, significantly reduced mixed cell aggregates. GE12 did not affect platelet aggregation induced by PMN-derived supernatants, indicating that the inhibitory effect of GE12 on mixed cell aggregation depends on inhibition of PMN/platelet adhesion. GE12 significantly reduced TxB₂ and LTC₄ production in PMN/platelet mixed cell suspensions stimulated by fMLP. As previously reported, synthesis of ³H-TxB₂ in ³H-AA-labeled PMN/unlabeled platelets indicates that platelets utilize ³H-AA from PMN. ³H-LTC₄ production in unlabeled PMN/³H-AA-labeled platelets indicates that bidirectional routes are utilized in this system for LTC₄ synthesis. GE12 significantly reduced ³H-TxB₂ and ³H-LTC₄ synthesis. These results show that cathepsin G released by activated PMN induces the expression of P-selectin on platelet membrane: this adhesive glycoprotein modulates cell-cell contact and transcellular metabolism of AA.

• References

• 1 Marcus AJ. Thrombosis and inflammation as multicellular processes: pathophysiologic significance of transcellular metabolism. Blood 1990; 76: 1903-1907
• 2 Marcus AJ. Eicosanoid interactions between platelets, endothelial cells and neutrophils. Methods Enzymol 1990; 187: 585-599
• 3 Chignard M, Selak MA, Smith JB. Direct evidence for the existence of a neutrophil-derived platelet activator (neutrophilin). Proc Natl Acad Sci USA 1986; 83: 8609-8613
• 4 Selak MA, Chignard M, Smith JB. Cathepsin G is a strong platelet agonist released by neutrophils. Biochem J 1988; 251: 293-299
• 5 Del Maschio A, Evangelista V, Rajtar G, Chen ZM, Cerletti C, de Gaetano G. Platelet activation induced by polymorphonuclear leukocytes exposed to chemotactic agents. Am J Physiol 1990; 258: H870-H879
• 6 Ferrer-Lopez P, Renesto P, Schattner M, Bassot MS, Laurent P, Chignard M. Activation of human platelets by C5a-stimulated neutrophils: a role for cathepsin G. Am J Physiol 1990; 258: Cl100-C1107
• 7 Evangelista V, Rajtar G, de Gaetano G, White JG, Cerletti C. Platelet activation by fMLP-stimulated polymorphonuclear leucocytes: the activity of cathepsin G is not prevented by antiproteinases. Blood 1991; 77: 2379-2388
• 8 Molino M, Di Lallo M, de Gaetano G, Cerletti C. Intracellular Ca²⁺ rise in human platelets induced by polymorphonuclear-leukocyte-derived cathepsin G. Biochem J 1992; 288: 741-745
• 9 Maugeri N, Evangelista V, Piccardoni P, Dell’lba G, Celardo A, de Gaetano G, Cerletti C. Transcellular metabolism of arachidonic acid: increased platelet thromboxane generation in the presence of activated polymorphonuclear leukocytes. Blood 1992; 80: 447-451
• 10 Maclouf JA, Murphy RC. Transcellular metabolism of neutrophil-derived leukotriene A₄ by human platelets. A potential cellular source of leuko-triene C₄ . J Biol Chem 1988; 263: 174-181
• 11 Fiore S, Serhan CN. Formation of lipoxins and leukotrienes during receptor-mediated interactions of human platelets and recombinant human granulocyte/macrophage colony-stimulating factor-primed neutrophils. J Exp Med 1990; 172: 1451-1457
• 12 Antoine C, Murphy RC, Henson PM, Maclouf J. Time-dependent utilization of platelet arachidonic acid by the neutrophil in formation of 5-lipoxygenase products in platelet-neutrophil co-incubations. Biochim Biophys Acta 1992; 1128: 139-146
• 13 Palmantier R, Borgeat P. Transcellular metabolism of arachidonic acid in platelets and polymorphonuclear leucocytes activated by physiological agonists: enhancement of leukotriene B₄ synthesis. Adv Exp Med Biol 1991; 314: 73-89
• 14 Brady RH, Serhan CN. Adhesion promotes transcellular leukotriene biosynthesis during neutrophil-glomerular endothelial cell interactions: inhibition by antibodies against CD 18 and L-selectin. Biochem Biophys Res Commun 1992; 186: 1307-1314
• 15 Bevilacqua M, Butcher E, Furie B, Gallatin M, Gimbrone M, Harlan J, Kishimoto K, Lasky L, McEver R, Paulson J, Rosen S, Seed B, Siegelman M, Springer T, Stoolman L, Tedder T, Varki A, Wagner D, Weissman I, Zimmerman G. Selectins: a family of adhesion receptors. Cell 1991; 67: 233
• 16 Larsen E, Celi A, Gilbert GE, Erban JK, Bonfanti R, Wagner DD, Furie B. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 1989; 59: 305-312
• 17 Hamburger SA, McEver RP. GMP-140 mediates adhesion of stimulated platelets to neutrophils. Blood 1990; 75: 550-554
• 18 Corraly LM, Singer S, Macher BA, Rosen SD. Requirement for sialic acid on neutrophils in a GMP-140 (PADGEM) mediated adhesive interaction with activated platelets. Biochem Biophys Res Commun 1990; 172: 1349-1356
• 19 Moore KL, Varki A, McEver RP. GMP-140 binds to a glycoprotein receptor on human neutrophils: evidence for a lectin-like interaction. J Cell Biol 1991; 112: 491-499
• 20 Polley MJ, Phillips ML, Wayner E, Nudelman E, Singhal AK, Hakomori S-I, Paulson JC. CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x. Proc Natl Acad Sci USA 1991; 88: 6224-6228
• 21 Zhou Q, Moore KL, Smith DF, Varki A, McEver RP, Cummings RD. The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells. J Cell Biol 1991; 115: 557-564
• 22 Foxall C, Watson SR, Dowbenko D, Fennie C, Lasky LA, Kiso M, Hasega-wa A, Asa D, Brandley BK. The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewisx oligosaccharide. J Cell Biol 1992; 117: 895-902
• 23 Norgard KE, Moore KL, Diaz S, Stults NL, Ushiyama S, McEver RP, Cummings RD, Varki A. Characterization of a specific ligand for P-selectin on myeloid cells. A minor glycoprotein with sialylated o-linked oligosaccharides. J Biol Chem 1993; 268: 12764-12774
• 24 Palabrica TR, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu Y-M, Sajer SA, Furie B. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature 1992; 359: 848-851
• 25 Powell WS. Reversed-phase high-pressure liquid chromatography of ara-chidonic acid metabolites formed by cyclooxygenase and lipoxygenases. Analyt Biochem 1985; 148: 59-69
• 26 Tordjman C, Serkiz B, Rambaud F, Bonnet J, Volland J. High-performance liquid chromatographic quantitation of cyclooxygenase and lipoxygenase metabolites of arachidonic acid from rat polymorphonuclear leukocytes. J Chromatogr 1990; 532: 135-143
• 27 Maclouf J, Murphy RC, Henson PM. Transcellular biosynthesis of sulfido-peptide leukotrienes during receptor-mediated stimulation of human neutrophil/platelet mixtures. Blood 1990; 76: 1838-1844
• 28 Evangelista V, Piccardoni P, White JG, de Gaetano G, Cerletti C. Cathep-sin G-dependent platelet stimulation by activated polymorphonuclear leukocytes and its inhibition by antiproteinases: role of P-selectin-mediated cell-cell adhesion. Blood 1993; 81: 2947-2957
• 29 Rouzer CA, Kargman S. Translocation of 5-lipoxygenase to the membrane in human leukocytes challenged with ionophore A23187. J Biol Chem 1988; 263: 10980-10988
• 30 Marcus AJ, Broekman MJ, Safier LB, Ullman HL, Islam N. Formation of leukotrienes and other hydroxy acids during platelet-neutrophil interactions in vitro. Biochem Biophys Res Commun 1982; 109: 130-137
• 31 Palmantier R, Borgeat P. Thrombin-activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists. BrJ Pharmacol 1991; 103: 1909-1916
• 32 Serhan CN, Sheppard K-A. Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A₄ by platelet 12-lipoxygenase in vitro. J Clin Invest 1990; 85: 772-780
• 33 Lewis RA, Austen KF, Soberman RJ. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med 1990; 323: 645-655
• 34 Spangenberg P, Redlich H, Bergmann I, Lösche W, Götzrath M, Kehrel B. The platelet glycoprotein Ilb/IIIa complex is involved in the adhesion of activated platelets to leukocytes. Thromb Haemost 1993; 70: 514-521
• 35 Silverstein RL, Nachman RL. Thrombospondin binds to monocytes-macro-phages and mediates platelet-monocyte adhesion. J Clin Invest 1987; 79: 867-874