Download PDF
Thromb Haemost 1997; 78(02): 919-925
DOI: 10.1055/s-0038-1657652
Rapid Communication
Schattauer GmbH Stuttgart

Different Requirement of Intracellular Calcium and Protein Kinase C for Arachidonic Acid Release and Serotonin Secretion in Cathepsin G-activated Platelets

Serenella Rotondo
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Virgilio Evangelista
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Stefano Manarini
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Giovanni de Gaetano
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Chiara Cerletti
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
› Author Affiliations
Further Information

Publication History

Received 08 1996

Accepted after revision 19 March 1997

Publication Date:
12 July 2018 (online)

 PDF Download  Permissions and Reprints

Summary

Previous studies have shown that platelet stimulation with cathepsin G rapidly results in cytoplasmic calcium ([Ca2+]j) increase and activation of protein kinase C (PKC). To elucidate the relationship between these two biochemical events and their relative contribution to the regulation of platelet response to cathepsin G, arachidonic acid (AA) release and serotonin (5HT) secretion were studied. Platelets made Ca2+- depleted and -permeable by treatment with A23187 were compared to intact platelets to better dissociate calcium changes from other receptor- stimulated events. AA release elicited by cathepsin G in intact platelets was prevented by the Ca2+ chelator BAPTA; in Ca2+-depleted, -permeable platelets AA was released in direct response to added Ca2+ and was not increased by simultaneous stimulation with cathepsin G. In intact platelets, PKC inhibition by Ro 31-8220 or PKC induction with PMA either enhanced or reduced, respectively, cathepsin G-induced AA release. Both BAPTA and Ro 31-8220 prevented 5HT secretion from intact platelets; however, in Ca2+-depleted, -permeable platelets, cathepsin G was able to evoke 5HT secretion and p47 phosphorylation independently of [Ca2+]j increase, both effects being hampered by Ro 31-8220. Ca2+ and PKC therefore regulate PLA2 activity and 5HT secretion in cathepsin G-stimulated platelets in a different manner: the former is mainly triggered by [Ca2+]j increase, while PKC represents the major factor in determining dense granule secretion.

 

  • References

  • 1 Marcus AJ, Safier LB, Broekman MJ, Naziba I, Fliessbach JH, Hajjar KA, Kaminski WE, Jendraschak E, Silverstein RL, von SchackyC. Thrombosis and inflammation as multicellular processes: significance of cell-cell interactions. Thromb Haemost 1995; 74: 213-217
    Thieme ConnectPubMedSearch in Google Scholar
  • 2 Henson PM. Interactions between neutrophils and platelets. Lab Invest 1990; 62: 391-393
    PubMedSearch in Google Scholar
  • 3 Faint RW. Platelet-neutrophil interactions: their significance. Blood Rev 1992; 06: 83-91
    CrossrefPubMedSearch in Google Scholar
  • 4 Kolpakov V, D’Adamo MC, Salvatore L, Amore C, Mironov A, Iacoviello L, Donati MB. Neutrophil-derived cathepsin G induces potentially throm- bogenic changes in human endothelial cells: a scanning electron microscopy study in static and dynamic conditions. Thromb Haemost 1994; 72: 140-145
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Cerletti C, Evangelista V, Molino M, de GaetanoG. Platelet activation by polymorphonuclear leukocyte: role of cathepsin G and P-selectin. Thromb Haemost 1995; 74: 213-217
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Selak MA, Chignard M, Smith JB. Cathepsin G is a strong platelet agonist released by neutrophils. Biochem J 1988; 251: 293-299
    CrossrefPubMedSearch in Google Scholar
  • 7 Ferrer-Lopez P, Renesto P, Schattner M, Bassot S, Laurent P, Chignard M. Activation of human platelets by C5a-stimulated neutrophils: a role for cathepsin G. Am J Physiol 1990; 258: Cl100-C1107
    PubMedSearch in Google Scholar
  • 8 Renesto P, Ferrer-Lopez P, Chignard M. Interference of recombinant eglin C, a proteinase inhibitor extracted from leeches, with neutrophil-mediated platelet activation. Lab Invest 1990; 62: 409-416
    PubMedSearch in Google Scholar
  • 9 Evangelista V, Rajtar G, de GaetanoG, White JG, Cerletti C. Platelet activation by fMLP-stimulated polymorphonuclear leukocytes: the activity of cathepsin G is not prevented by antiproteinases. Blood 1991; 77: 2379-2388
    PubMedSearch in Google Scholar
  • 10 Evangelista V, Piccardoni P, White JG, de GaetanoG, Cerletti C. Cathepsin 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
    PubMedSearch in Google Scholar
  • 11 Selak MA, Smith JB. Cathepsin G binding to human platelets. Evidence for a specific receptor. Biochem J 1990; 266: 55-62
    CrossrefPubMedSearch in Google Scholar
  • 12 Selak MA. Cathepsin G and thrombin: evidence for two different platelet receptors. Biochem J 1994; 297: 269-265
    CrossrefPubMedSearch in Google Scholar
  • 13 Molino M, Di LalloM, de GaetanoG, Cerletti C. Intracellular Ca2+rise in human platelets induced by polymorphonuclear-leucocyte-derived cathepsin G. Biochem J 1992; 288: 741-745
    CrossrefPubMedSearch in Google Scholar
  • 14 Molino M, Di LalloM, de GaetanoG, Cerletti C. Platelet protein kinase C (PKC) activation by neutrophil-derived cathepsin G. Thromb Haemost 1993; 69: 1163 (Abstract)
    PubMedSearch in Google Scholar
  • 15 Si-Tahar M, Renesto P, Falet H, Rendu F, Chignard M. The phospholipase C/protein kinase C pathway is involved in cathepsin G-induced human platelet activation: comparison with thrombin. Biochem J 1996; 313: 401-408
    CrossrefPubMedSearch in Google Scholar
  • 16 Maugeri N, Evangelista V, Celardo A, Dell’Elba G, Martelli N, Piccardoni P, de GaetanoG, Cerletti C. Polymorphonuclear leukocyte-platelet interaction: role of P-selectin in thromboxane B2and leukotriene C4cooperative synthesis. Thromb Haemost 1994; 72: 450-456
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+indicators with greatly improved fluorescence properties. J Biol Chem 1985; 260: 3440-3450
    PubMedSearch in Google Scholar
  • 18 Fabiato A, Fabiato F. Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol 1979; 75: 463-505
    PubMedSearch in Google Scholar
  • 19 Goodwin BJ, Weinberg JB. Receptor-mediated modulation of human monocyte, neutrophil, lymphocyte, and platelet function by phorbol diesters. J Clin Invest 1982; 70: 699-706
    CrossrefPubMedSearch in Google Scholar
  • 20 Wolf M, LeVine IIIH, May Jr WS, Cuatrecasas P, Sahyoun N. A model for intracellular translocation of protein kinase C involving synergism between Ca2+and phorbol esters. Nature 1985; 317: 546-549
    CrossrefPubMedSearch in Google Scholar
  • 21 Kiley S, Schaap D, Parker P, Hsieh L-L, Jaken S. Protein kinase C heterogeneity in GH4Ctrat pituitary cells. Characterization of a Ca2+-independent phorbol ester receptor. J Biol Chem 1990; 265: 15704-15712
    PubMedSearch in Google Scholar
  • 22 Takaya J, Kimura M, Lasker N, Aviv A. Phorbol 12,13-dibutyrate binding to intact human platelets. The role of cytosolic free Ca2+ . Biochem J 1991; 278: 411-415
    CrossrefPubMedSearch in Google Scholar
  • 23 Siess W, Lapetina EG. Ca2+mobilization primes protein kinase C in human platelets. Ca2+and phorbol esters stimulate platelet aggregation and secretion synergistically through protein kinase C. Biochem J 1988; 255: 309-318
    PubMedSearch in Google Scholar
  • 24 Mayer AMS, Glaser KB, Jacobs RS. Regulation of eicosanoid biosynthesis in vitro and in vivo by the marine natural product manoalide: a potent inactivator of venom phospholipases. J Pharmacol Exp Ther 1988; 244: 871-878
    PubMedSearch in Google Scholar
  • 25 Halenda SP, Rehm AG. Thrombin and C-kinase activators potentiate calcium-stimulated arachidonic acid release in human platelets. Biochem J 1987; 248: 471-475
    CrossrefPubMedSearch in Google Scholar
  • 26 Molino M, Di LalloM, Martelli N, de GaetanoG, Cerletti C. Effects of leukocyte-derived cathepsin G on platelet membrane glycoprotein Ib-IX and nb-IDa complexes: a comparison with thrombin. Blood 1993; 82: 2442-2451
    PubMedSearch in Google Scholar
  • 27 Kroll HK, Schafer AI. Biochemical mechanisms of platelet activation. Blood 1989; 74: 1181-1195
    PubMedSearch in Google Scholar
  • 28 Davis PD, Hill CH, Keech E, Lawton G, Nixon JS, Sedgwick AD, Wadsworth J, Westmacott D, Wilkinson SE. Potent selective inhibitors of protein kinase C. FEBS Lett 1989; 259: 61-63
    CrossrefPubMedSearch in Google Scholar
  • 29 Tyers M, Rachubinski RA, Stewart MI, Varrichio AM, Shorr RGL, Haslam RJ, Harley CB. Molecular cloning and expression of the major protein kinase C substrate of platelets. Nature 1988; 333: 470-473
    CrossrefPubMedSearch in Google Scholar
  • 30 Naka M, Nishikawa M, Adelstein RS, Hidaka H. Phorbol ester-induced activation of human platelets is associated with protein kinase C phosphorylation of myosin light chains. Nature 1983; 306: 490-492
    CrossrefPubMedSearch in Google Scholar
  • 31 Nishizuka Y. Studies and perspectives of protein kinase C. Science 1986; 233: 305-312
    CrossrefPubMedSearch in Google Scholar
  • 32 Walker TR, Watson SP. Synergy between Ca2+and protein kinase C is the major factor in determining the level of secretion from human platelets. Biochem J 1993; 289: 277-282
    CrossrefPubMedSearch in Google Scholar
  • 33 Zavoico GB, Halenda SP, Sha’afi RI, Feinstein MB. Phorbol myristate acetate inhibits thrombin-stimulated Ca2+mobilization and phosphatidyl- inositol 4,5-bisphosphate hydrolysis in human platelets. Proc Natl Acad Sci USA 1985; 82: 3859-3862
    CrossrefPubMedSearch in Google Scholar
  • 34 Murayama T, Kajiyama Y, Takahashi A, Nomura Y. Modes of inhibitory action of 4B-phorbol 12-myristate 13-acetate in thrombin-stimulated arachidonic acid release in intact and permeabilized platelets. Arch Biochem Biophys 1990; 276: 146-152
    CrossrefPubMedSearch in Google Scholar
  • 35 Murphy CT, Westwick J. Selective inhibition of protein kinase C. Effect on platelet-activating-factor-induced platelet responses. Biochem J 1992; 283: 159-164
    PubMedSearch in Google Scholar
  • 36 Lin L-L, Wartman M, Lin AL, Knopf JL, Seth A, Davis RJ. cPLA2is phos- phorylated and activated by MAP kinase. Cell 1993; 72: 269-278
    CrossrefPubMedSearch in Google Scholar
  • 37 Börsch-Haubold AG, Kramer RM, Watson SP. Cytosolic phospholipase A2is phosphorylated in collagen and thrombin-stimulated human platelets independent of protein kinase C and mitogen-activated protein kinase. J Biol Chem 1995; 270: 25885-25892
    CrossrefPubMedSearch in Google Scholar
  • 38 Hargreaves PG, Licking EF, Sargeant P, Sage SO, Barnes MJ, Famdale RW. The tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycin-namate, inhibit the release of (3H) arachidonate from human platelets stimulated by thrombin or collagen. Thromb Haemost 1994; 72: 634-642
    Thieme ConnectPubMedSearch in Google Scholar
  • 39 Hargreaves PG, Jenner S, Merritt JE, Sage SO, Famdale RW. Ionomycin- stimulated arachidonic acid release in human platelets: a role for protein kinase C and tyrosine phosphorylation. Thromb Haemost 1996; 76: 248-252
    Thieme ConnectPubMedSearch in Google Scholar
  • 40 Huang K-P. The mechanism of protein kinase activation. Trends Neurosci 1989; 12: 425-432
    CrossrefPubMedSearch in Google Scholar