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Platelet Physiology

  • Chapter
Platelet Function

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Platelets are anucleate circulating blood particles. They circulate around the body in an inactive state until they come into contact with areas of endothelial damage or activation of the coagulation cascade. Here they adhere to the endothelial defect, change shape, release their granule contents, and stick together to form aggregates. Physiologically these processes help to limit blood loss; however, inappropriate or excessive platelet activation results in an acute obstruction of blood flow, as occurs, for example, in an acute myocardial infarction. However, activated platelets also express and release molecules that stimulate a localized inflammatory response through the activation of leukocytes and endothelial cells, and it is now clear that platelet function is not merely limited to the prevention of blood loss. Indeed, platelets have been implicated in many pathological processes including host defense, inflammatory arthritis, adult respiratory distress syndrome, and tumor growth and metastasis. In this chapter I review our current understanding of platelet physiology in order to provide a global background for the more in-depth focused chapters later in this book.

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References

  1. Kroll MH, Hellums JD, McIntire LV, Schafer AI, Moake JL. Platelets and shear stress. Blood 1996;88:1525–1541.

    PubMed  CAS  Google Scholar 

  2. Wenzel UO, Fouqueray B, Grandaliano G, et al. Thrombin regulates expression of monocyte chemoattractant protein-1 in vascular smooth muscle cells. Circ Res 1995;77:503–509.

    PubMed  CAS  Google Scholar 

  3. DeMichele MA, Moon DG, Fenton JW, 2nd, Minnear FL. Thrombin’s enzymatic activity increases permeability of endothelial cell monolayers. J Appl Physiol 1990;69:1599–1606.

    PubMed  CAS  Google Scholar 

  4. Kranzhofer R, Clinton SK, Ishii K, Coughlin SR, Fenton JW, 2nd, Libby P. Thrombin potently stimulates cytokine production in human vascular smooth muscle cells but not in mononuclear phagocytes. Circ Res 1996;79:286–294.

    PubMed  CAS  Google Scholar 

  5. McNamara CA, Sarembock IJ, Gimple LW, Fenton JW, 2nd, Coughlin SR, Owens GK. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. J Clin Invest 1993;91:94–98.

    PubMed  CAS  Google Scholar 

  6. Haralabopoulos GC, Grant DS, Kleinman HK, Maragoudakis ME. Thrombin promotes endothelial cell alignment in Matrigel in vitro and angiogenesis in vivo. Am J Physiol 1997;273:C239–C245.

    PubMed  CAS  Google Scholar 

  7. Griffin CT, Srinivasan Y, Zheng YW, Huang W, Coughlin SR. A role for thrombin receptor signaling in endothelial cells during embryonic development. Science 2001;293:1666–1670.

    PubMed  CAS  Google Scholar 

  8. Connolly AJ, Ishihara H, Kahn ML, Farese RV Jr, Coughlin SR. Role of the thrombin receptor in development and evidence for a second receptor. Nature 1996;381:516–519.

    PubMed  CAS  Google Scholar 

  9. Molino M, Bainton DF, Hoxie JA, Coughlin SR, Brass LF. Thrombin receptors on human platelets. Initial localization and subsequent redistribution during platelet activation. J Biol Chem 1997;272:6011–6017.

    PubMed  CAS  Google Scholar 

  10. Chen J, Ishii M, Wang L, Ishii K, Coughlin SR. Thrombin receptor activation. Confirmation of the intramolecular tethered liganding hypothesis and discovery of an alternative intermolecular liganding mode. J Biol Chem 1994;269:16041–16045.

    PubMed  CAS  Google Scholar 

  11. Vu TK, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991;64:1057–1068.

    PubMed  CAS  Google Scholar 

  12. Kahn ML, Zheng YW, Huang W, et al. A dual thrombin receptor system for platelet activation. Nature 1998;394:690–694.

    PubMed  CAS  Google Scholar 

  13. Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 1999;103:879–887.

    PubMed  CAS  Google Scholar 

  14. Shapiro MJ, Weiss EJ, Faruqi TR, Coughlin SR. Protease-activated receptors 1 and 4 are shut off with distinct kinetics after activation by thrombin. J Biol Chem 2000;275:25216–25221.

    PubMed  CAS  Google Scholar 

  15. Nakanishi-Matsui M, Zheng YW, Sulciner DJ, Weiss EJ, Ludeman MJ, Coughlin SR. PAR3 is a cofactor for PAR4 activation by thrombin. Nature 2000;404:609–613.

    PubMed  CAS  Google Scholar 

  16. Kim S, Foster C, Lecchi A, et al. Protease-activated receptors 1 and 4 do not stimulate G(i) signaling pathways in the absence of secreted ADP and cause human platelet aggregation independently of G(i) signaling. Blood 2002;99:3629–3636.

    PubMed  CAS  Google Scholar 

  17. Soslau G, Class R, Morgan DA, et al. Unique pathway of thrombin-induced platelet aggregation mediated by glycoprotein Ib. J Biol Chem 2001;276:21173–21183.

    PubMed  CAS  Google Scholar 

  18. Li CQ, Vindigni A, Sadler JE, Wardell MR. Platelet glycoprotein Ib alpha binds to thrombin anion-binding exosite II inducing allosteric changes in the activity of thrombin. J Biol Chem 2001;276:6161–6168.

    PubMed  CAS  Google Scholar 

  19. De Candia E, Hall SW, Rutella S, Landolfi R, Andrews RK, De Cristofaro R. Binding of thrombin to glycoprotein Ib accelerates the hydrolysis of Par-1 on intact platelets. J Biol Chem 2001;276:4692–4698.

    PubMed  Google Scholar 

  20. Tsuji M, Ezumi Y, Arai M, Takayama H. A novel association of Fc receptor gammachain with glycoprotein VI and their co-expression as a collagen receptor in human platelets. J Biol Chem 1997;272:23528–23531.

    PubMed  CAS  Google Scholar 

  21. Locke D, Chen H, Liu Y, Liu C, Kahn ML. Lipid rafts orchestrate signaling by the platelet receptor glycoprotein VI. J Biol Chem 2002;277:18801–18809.

    PubMed  CAS  Google Scholar 

  22. Ezumi Y, Kodama K, Uchiyama T, Takayama H. Constitutive and functional association of the platelet collagen receptor glycoprotein VI-Fc receptor gamma-chain complex with membrane rafts. Blood 2002;99:3250–3255.

    PubMed  CAS  Google Scholar 

  23. Kehrel B, Wierwille S, Clemetson KJ, et al. Glycoprotein VI is a major collagen receptor for platelet activation: it recognizes the platelet-activating quaternary structure of collagen, whereas CD36, glycoprotein IIb/IIIa, and von Willebrand factor do not. Blood 1998;91:491–499.

    PubMed  CAS  Google Scholar 

  24. Poole A, Gibbins JM, Turner M, et al. The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO J 1997;16:2333–2341.

    PubMed  CAS  Google Scholar 

  25. Cicmil M, Thomas JM, Leduc M, Bon C, Gibbins JM. Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets. Blood 2002;99:137–144.

    PubMed  CAS  Google Scholar 

  26. Larson MK, Chen H, Kahn ML, et al. Identification of P2Y12-dependent and — independent mechanisms of glycoprotein VI-mediated Rap1 activation in platelets. Blood 2003;101:1409–1415.

    PubMed  CAS  Google Scholar 

  27. Cho MJ, Liu J, Pestina TI, et al. The roles of alpha IIb beta 3-mediated outside-in signal transduction, thromboxane A2, and adenosine diphosphate in collagen-induced platelet aggregation. Blood 2003;101:2646–26451.

    PubMed  CAS  Google Scholar 

  28. Reilly M, Fitzgerald GA. Cellular activation by thromboxane A2 and other eicosanoids. Eur Heart J 1993;14:88–93.

    PubMed  CAS  Google Scholar 

  29. FitzGerald GA. Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. Am J Cardiol 1991;68:11B–15B.

    PubMed  CAS  Google Scholar 

  30. Hirata T, Ushikubi F, Kakizuka A, Okuma M, Narumiya S. Two thromboxane A2 receptor isoforms in human platelets. Opposite coupling to adenylyl cyclase with different sensitivity to Arg60 to Leu mutation. J Clin Invest 1996;97:949–956.

    PubMed  CAS  Google Scholar 

  31. Narumiya S. Structures, properties and distributions of prostanoid receptors. Adv Prostaglandin Thromboxane Leukotriene Res 1995;23:17–22.

    CAS  Google Scholar 

  32. Halushka PV, Allan CJ, Davis-Bruno KL. Thromboxane A2 receptors. J Lipid Mediators Cell Signal 1995;12:361–378.

    CAS  Google Scholar 

  33. Meyers KM, Holmsen H, Seachord CL. Comparative study of platelet dense granule constituents. Am J Physiol 1982;243:R454–R461.

    PubMed  CAS  Google Scholar 

  34. Gardner A, Jonsen J, Laland S, Hellem A, Owren P. Adenosine diphosphate in red blood cells as a factor in the adhesiveness of human blood platelets. Nature 1961;192:531–532.

    Google Scholar 

  35. Hollopeter G, Jantzen HM, Vincent D, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001;409:202–207.

    PubMed  CAS  Google Scholar 

  36. Jin J, Daniel JL, Kunapuli SP. Molecular basis for ADP-induced platelet activation. II. The P2Y1 receptor mediates ADP-induced intracellular calcium mobilization and shape change in platelets. J Biol Chem 1998;273:2030–2034.

    PubMed  CAS  Google Scholar 

  37. Sun B, Li J, Okahara K, Kambayashi J. P2X1 purinoceptor in human platelets. Molecular cloning and functional characterization after heterologous expression. J Biol Chem 1998;273:11544–11547.

    PubMed  CAS  Google Scholar 

  38. Savi P, Bornia J, Salel V, Delfaud M, Herbert JM. Characterization of P2x1 purinoreceptors on rat platelets: effect of clopidogrel. Br J Haematol 1997;98:880–886.

    PubMed  CAS  Google Scholar 

  39. Oury C, Toth-Zsamboki E, Vermylen J, Hoylaerts MF. P2X(1)-mediated activation of extracellular signal-regulated kinase 2 contributes to platelet secretion and aggregation induced by collagen. Blood 2002;100:2499–2505.

    PubMed  CAS  Google Scholar 

  40. Daniel J, Dangelmaier C, Jin J, Ashby B, Smith J, Kunapuli S. Molecular basis for ADP-induced platelet activation: evidence for three distinct ADP receptors on human platelets. J Biol Chem 1998;273:2024–2029.

    PubMed  CAS  Google Scholar 

  41. Jin J, Quinton TM, Zhang J, Rittenhouse SE, Kunapuli SP. Adenosine diphosphate (ADP)-induced thromboxane A(2) generation in human platelets requires coordinated signaling through integrin alpha(IIb)beta(3) and ADP receptors. Blood 2002;99:193–198.

    PubMed  CAS  Google Scholar 

  42. Kauffenstein G, Bergmeier W, Eckly A, et al. The P2Y(12) receptor induces platelet aggregation through weak activation of the alpha(IIb)beta(3) integrin—a phosphoinositide 3-kinase-dependent mechanism. FEBS Lett 2001;505:281–290.

    PubMed  CAS  Google Scholar 

  43. Ding Z, Kim S, Dorsam RT, Jin J, Kunapuli SP. Inactivation of the human P2Y12 receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cys17 and Cys270. Blood 2003;101:3908–3914.

    PubMed  CAS  Google Scholar 

  44. Li Z, Xi X, Du X. A mitogen-activated protein kinase-dependent signaling pathway in the activation of platelet integrin alpha IIbbeta3. J Biol Chem 2001;276:42226–42232.

    PubMed  CAS  Google Scholar 

  45. Brass LF, Manning DR, Cichowski K, Abrams CS. Signaling through G proteins in platelets: to the integrins and beyond. Thromb Haemost 1997;78:581–589.

    PubMed  CAS  Google Scholar 

  46. Dorsam RT, Kim S, Jin J, Kunapuli SP. Coordinated signaling through both G12/13 and G(i) pathways is sufficient to activate GPIIb/IIIa in human platelets. J Biol Chem 2002;277:47588–47595.

    PubMed  CAS  Google Scholar 

  47. Nieswandt B, Schulte V, Zywietz A, Gratacap MP, Offermanns S. Costimulation of Gi-and G12/G13-mediated signaling pathways induces integrin alpha IIbbeta 3 activation in platelets. J Biol Chem 2002;277:39493–39498.

    PubMed  CAS  Google Scholar 

  48. Nadal-Wollbold F, Pawlowski M, Levy-Toledano S, Berrou E, Rosa JP, Bryckaert M. Platelet ERK2 activation by thrombin is dependent on calcium and conventional protein kinases C but not Raf-1 or B-Raf. FEBS Lett 2002;531:475–482.

    PubMed  CAS  Google Scholar 

  49. Blockmans D, Deckmyn H, Vermylen J. Platelet activation. Blood Rev 1995;9:143–156.

    PubMed  CAS  Google Scholar 

  50. Kovacsovics T, Bachelot C, Toker A, et al. Phosphoinositide 3-kinase inhibition spares actin assembly in activating platelets but reverses platelet aggregation. J Biol Chem 1995;270:11358–11366.

    PubMed  CAS  Google Scholar 

  51. Hmama Z, Knutson K, Herrera-Velit P, Nandan D, Reiner N. Monocyte adherence induced by lipopolysaccharide involves CD14, LFA-1, and cytohesin-1. Regulation by Rho and phosphatidylinositol 3-kinase. J Biol Chem 1999;274:1050–1057.

    PubMed  CAS  Google Scholar 

  52. Toker A, Cantley L. Signalling through the lipid products of phosphoinositide-3-OH kinase. Nature 1997;387:673–676.

    PubMed  CAS  Google Scholar 

  53. Fujimoto TT, Katsutani S, Shimomura T, Fujimura K. Thrombospondin-bound integrin associated protein (CD47) physically and functionally modifies integrin alpha IIbbeta 3 by its extracellular domain. J Biol Chem 2003;7:7.

    Google Scholar 

  54. Lagadec P, Dejoux O, Ticchioni M, et al. Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow. Blood 2003;101:4836–4843.

    PubMed  CAS  Google Scholar 

  55. Henn V, Slupsky JR, Grafe M, et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998;391:591–594.

    PubMed  CAS  Google Scholar 

  56. Keenan J, Solum N. Quantitative studies on the release of platelet fibrinogen by thrombin. Br J Haematol 1972;23:461–466.

    PubMed  CAS  Google Scholar 

  57. Dale GL, Friese P, Batar P, et al. Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. Nature 2002;415:175–179.

    PubMed  CAS  Google Scholar 

  58. Polgar J, Chung SH, Reed GL. Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion. Blood 2002;100:1081–1083.

    PubMed  CAS  Google Scholar 

  59. Merten M, Pakala R, Thiagarajan P, Benedict C. Platelet microparticles promote platelet interaction with subendothelial matrix in a glycoprotein IIb/IIIa-dependent mechanism. Circulation 1999;99:2577–2582.

    PubMed  CAS  Google Scholar 

  60. Barry O, Kazanietz M, Pratico D, FitzGerald G. Arachidonic acid in platelet microparticles up-regulates cyclooxygenase-2-dependent prostaglandin formation via a protein kinase C/mitogen-activated protein kinase-dependent pathway. J Biol Chem 1999;274:7545–7556.

    PubMed  CAS  Google Scholar 

  61. Andrews RK, Shen Y, Gardiner EE, Dong JF, Lopez JA, Berndt MC. The glycoprotein Ib-IX-V complex in platelet adhesion and signaling. Thromb Haemost 1999;82:357–364.

    PubMed  CAS  Google Scholar 

  62. Matsui H, Sugimoto M, Mizuno T, et al. Distinct and concerted functions of von Willebrand factor and fibrinogen in mural thrombus growth under high shear flow. Blood 2002;100:3604–3610.

    PubMed  CAS  Google Scholar 

  63. Ruggeri ZM. von Willebrand factor. J Clin Invest 1997;99:559–564.

    PubMed  CAS  Google Scholar 

  64. Kasirer-Friede A, Ware J, Leng L, Marchese P, Ruggeri ZM, Shattil SJ. Lateral clustering of platelet GP Ib-IX complexes leads to up-regulation of the adhesive function of integrin alpha IIbbeta 3. J Biol Chem 2002;277:11949–11956.

    PubMed  CAS  Google Scholar 

  65. Zaffran Y, Meyer SC, Negrescu E, Reddy KB, Fox JE. Signaling across the platelet adhesion receptor glycoprotein Ib-IX induces alpha IIbbeta 3 activation both in platelets and a transfected Chinese hamster ovary cell system. J Biol Chem 2000;275:16779–16787.

    PubMed  CAS  Google Scholar 

  66. Bombeli T, Schwartz BR, Harlan JM. Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICAM-1), alphavbeta3 integrin, and GPIbalpha. J Exp Med 1998;187:329–339.

    PubMed  CAS  Google Scholar 

  67. Hermand P, Gane P, Huet M, et al. Red cell ICAM-4 is a novel ligand for platelet-activated alpha IIbbeta 3 integrin. J Biol Chem 2003;278:4892–4898.

    PubMed  CAS  Google Scholar 

  68. Shattil SJ, Hoxie JA, Cunningham M, Brass LF. Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation. J Biol Chem 1985;260:11107–11114.

    PubMed  CAS  Google Scholar 

  69. O’Toole T, Mandelman D, Forsyth J, Shattil SJ, Plow EF, Ginsberg MH. Modulation of the affinity of integrin alpha IIb beta 3 (GPIIb-IIIa) by the cytoplasmic domain of alpha IIb. Science 1991;254:845–847.

    PubMed  CAS  Google Scholar 

  70. O’Toole T, Katagiri Y, Faull RJ, et al. Integrin cytoplasmic domains mediate inside-out signal transduction. J Cell Biol 1994;124:1047–1059.

    PubMed  CAS  Google Scholar 

  71. Stephens G, O’Luanaigh N, Reilly D, et al. A sequence within the cytoplasmic tail of GpIIb independently activates platelet aggregation and thromboxane synthesis. J Biol Chem 1998;273:20317–20322.

    PubMed  CAS  Google Scholar 

  72. Leisner TM, Wencel-Drake JD, Wang W, Lam SCT. Bidirectional transmembrane modulation of integrin alpha IIb beta 3 conformations. J Biol Chem 1999:12945–12949.

    Google Scholar 

  73. Chen Y, O’Toole T, Shipley T, et al. “Inside-out” signal transduction inhibited by isolated integrin cytoplasmic domains. J Biol Chem 1994;269:18307–18310.

    PubMed  CAS  Google Scholar 

  74. Naik U, Patel P, Parise L. Identification of a novel calcium-binding protein that interacts with the integrin alphaIIb cytoplasmic domain. J Biol Chem 1997;272:4651–4654.

    PubMed  CAS  Google Scholar 

  75. Naik UP, Naik MU. Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen. Blood 2003;24:24.

    Google Scholar 

  76. Tsuboi S. Calcium integrin-binding protein activates platelet integrin alpha IIbbeta 3. J Biol Chem 2002;277:1919–1923.

    PubMed  CAS  Google Scholar 

  77. Bertoni A, Tadokoro S, Eto K, et al. Relationships between Rap1b, affinity modulation of integrin alpha IIbbeta 3, and the actin cytoskeleton. J Biol Chem 2002;277:25715–25721.

    PubMed  CAS  Google Scholar 

  78. Haataja L, Kaartinen V, Groffen J, Heisterkamp N. The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading. J Biol Chem 2002;277:8321–8328.

    PubMed  CAS  Google Scholar 

  79. Wagner CL, Mascelli MA, Neblock DS, Weisman HF, Coller BS, Jordan RE. Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to human platelets. Blood 1996;88:907–914.

    PubMed  CAS  Google Scholar 

  80. Hynes R. Integrins: a family of cell surface receptors. Cell 1987;48:549–554.

    PubMed  CAS  Google Scholar 

  81. Bray PF, Rosa JP, Johnston GI, et al. Platelet glycoprotein IIb. Chromosomal localization and tissue expression. J Clin Invest 1987;80:1812–1817.

    Article  PubMed  CAS  Google Scholar 

  82. Rosa JP, Bray PF, Gayet O, et al. Cloning of glycoprotein IIIa cDNA from human erythroleukemia cells and localization of the gene to chromosome 17. Blood 1988;72:593–600.

    PubMed  CAS  Google Scholar 

  83. Weisel J, Nagaswami C, Vilaire G, Bennett J. Examination of the platelet membrane glycoprotein IIb-IIIa complex and its interaction with fibrinogen and other ligands by electron microscopy. J Biol Chem 1992;267:16637–16643.

    PubMed  CAS  Google Scholar 

  84. Calvete JJ. On the structure and function of platelet integrin alpha IIb beta 3, the fibrinogen receptor. Proc Soc Exp Biol Med 1995;208:346–360.

    PubMed  CAS  Google Scholar 

  85. Springer T. An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components. J Mol Biol 1998;283:837–862.

    PubMed  CAS  Google Scholar 

  86. Xiong JP, Stehle T, Diefenbach B, et al. Crystal structure of the extracellular segment of integrin alpha Vbeta3. Science 2001;294:339–345.

    PubMed  CAS  Google Scholar 

  87. Kashiwagi H, Tomiyama Y, Tadokoro S, et al. A mutation in the extracellular cysteine-rich repeat region of the beta3 subunit activates integrins alphaIIbbeta3 and alphaVbeta3. Blood 1999;93:2559–2568.

    PubMed  CAS  Google Scholar 

  88. Sun QH, Liu CY, Wang R, Paddock C, Newman PJ. Disruption of the long-range GPIIIa Cys(5)-Cys(435) disulfide bond results in the production of constitutively active GPIIb-IIIa (alpha(IIb)beta(3)) integrin complexes. Blood 2002;100:2094–2101.

    PubMed  CAS  Google Scholar 

  89. Peeschke E. Regulation of platelet aggregation by post-fibrinogen binding. Insights provided by dithiothreitol treated platelets. Thromb Haemost 1995:862–867.

    Google Scholar 

  90. Gulino D, Boudignon C, Zhang L, Concord E, Rabiet M, Marguerie G. Ca(2+)-binding properties of the platelet glycoprotein IIb ligand-interacting domain. J Biol Chem 1992;267:1001–1007.

    PubMed  CAS  Google Scholar 

  91. Calvete J, Schafer W, Mann K, Henschen A, Gonzalez-Rodriguez J. Localization of the cross-linking sites of RGD and KQAGDV peptides to the isolated fibrinogen receptor, the human platelet integrin glycoprotein IIb/IIIa. Influence of peptide length. Eur J Biochem 1992;206:759–765.

    PubMed  CAS  Google Scholar 

  92. D’Souza S, Ginsberg M, Burke T, Plow E. The ligand binding site of the platelet integrin receptor GPIIb-IIIa is proximal to the second calcium binding domain of its alpha subunit. J Biol Chem 1990;265:3440–3446.

    PubMed  CAS  Google Scholar 

  93. D’Souza S, Ginsberg M, Matsueda G, Plow E. A discrete sequence in a platelet integrin is involved in ligand recognition. Nature 1991;350:66–68.

    PubMed  CAS  Google Scholar 

  94. Cierniewski CS, Byzova T, Papierak M, et al. Peptide ligands can bind to distinct sites in integrin alphaIIbbeta3 and elicit different functional responses. J Biol Chem 1999;274:16923–16932.

    PubMed  CAS  Google Scholar 

  95. Loftus J, O’Toole T, Plow E, Glass A, Frelinger A, Ginsberg M. A beta 3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation. Science 1990;249:915–918.

    PubMed  CAS  Google Scholar 

  96. Tozer E, Liddington R, Sutcliffe M, Smeeton A, Loftus J. Ligand binding to integrin alphaIIbbeta3 is dependent on a MIDAS-like domain in the beta3 subunit. Biol Chem 1996;271:21978–21984.

    CAS  Google Scholar 

  97. Yamada KM, Miyamoto S. Integrin transmembrane signaling and cytoskeletal control. Curr Opin Cell Biol 1995;7:681–689.

    PubMed  CAS  Google Scholar 

  98. Fox JE, Lipfert L, Clark EA, Reynolds CC, Austin CD, Brugge JS. On the role of the platelet membrane skeleton in mediating signal transduction. Association of GP IIb-IIIa, pp60c-src, pp62c-yes, and the p21ras GTPase-activating protein with the membrane skeleton. J Biol Chem 1993;268:25973–25984.

    PubMed  CAS  Google Scholar 

  99. Shattil S, Haimovich B, Cunningham M, et al J. Tyrosine phosphorylation of pp125FAK in platelets requires coordinated signaling through integrin and agonist recptors. J Biol Chem 1994;269:14738–14745.

    PubMed  CAS  Google Scholar 

  100. Kouns WC, Kirchhofer D, Hadvary P, et al. Reversible conformational changes induced in glycoprotein IIb-IIIa by a potent and selective peptidomimetic inhibitor. Blood 1992;80:2539–2547.

    PubMed  CAS  Google Scholar 

  101. Schaffner-Reckinger E, Gouon V, Melchior C, Plancon S, Kieffer N. Distinct involvement of beta3 integrin cytoplasmic domain tyrosine residues 747 and 759 in integrin-mediated cytoskeletal assembly and phosphotyrosine signaling. J Biol Chem 1998;273:12623–12632.

    PubMed  CAS  Google Scholar 

  102. Jenkins A, Nannizzi-Alaimo L, Silver D, et al. Tyrosine phosphorylation of the beta3 cytoplasmic domain mediates integrin-cytoskeletal interactions. J Biol Chem 1998;273:13878–13885.

    PubMed  CAS  Google Scholar 

  103. Law D, Nannizzi-Alaimo L, Phillips D. Outside-in integrin signal transduction. Alpha IIb beta 3-(GP IIb IIIa) tyrosine phosphorylation induced by platelet aggregation. J Biol Chem 1996;271:10811–10815.

    PubMed  CAS  Google Scholar 

  104. Obergfell A, Eto K, Mocsai A, et al. Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton. J Cell Biol 2002;157:265–275.

    PubMed  CAS  Google Scholar 

  105. Sorisky A, King W, Rittenhouse S. Accumulation of PtdIns(3,4)P2 and PtdIns(3,4,5)P3 in thrombin-stimulated platelets. Different sensitivities to Ca2+ or functional integrin. Biochem J 1992;286:581–584.

    PubMed  CAS  Google Scholar 

  106. Rittenhouse S. Phosphoinositide 3-kinase activation and platelet function. Blood 1996;89:4401–4414.

    Google Scholar 

  107. Toker A, Bachelot C, Chen C, et al. Phosphorylation of the platelet p47 phosphoprotein is mediated by the lipid products of phosphoinositide 3-kinase. J Biol Chem 1995;270:29525–29531.

    PubMed  CAS  Google Scholar 

  108. D’Souza S, Ginsberg MH, Burke TA, Lam SC, Plow EF. Localization of an Arg-Gly-Asp recognition site within an integrin adhesion receptor. Science 1988;242:91–93.

    PubMed  CAS  Google Scholar 

  109. D’Souza S, Ginsberg MH, Lam SC, Plow EF. Chemical cross-linking of arginylglycyl-aspartic acid peptides to an adhesion receptor on platelets. J Biol Chem 1988;263:3943–3951.

    PubMed  CAS  Google Scholar 

  110. Farrell DH, Thiagarajan P, Chung DW, Davie EW. Role of fibrinogen alpha and gamma chain sites in platelet aggregation. Proc Natl Acad Sci USA 1992;89:10729–10732.

    PubMed  CAS  Google Scholar 

  111. Holmback K, Danton MJ, Suh TT, Daugherty CC, Degen JL. Impaired platelet aggregation and sustained bleeding in mice lacking the fibrinogen motif bound by integrin alpha IIb beta 3. EMBO J 1996;15:5760–5771.

    PubMed  CAS  Google Scholar 

  112. Savage B, Bottini E, Ruggeri ZM. Interaction of integrin alpha IIb beta 3 with multiple fibrinogen domains during platelet adhesion. J Biol Chem 1995;270:28812–28817.

    PubMed  CAS  Google Scholar 

  113. Gawaz M, Neumann FJ, Dickfeld T, et al. Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells. Circulation 1998;98:1164–1171.

    PubMed  CAS  Google Scholar 

  114. Henn V, Steinbach S, Buchner K, Presek P, Kroczek RA. The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40. Blood 2001;98:1047–1054.

    PubMed  CAS  Google Scholar 

  115. Lutgens E, Cleutjens KB, Heeneman S, Koteliansky VE, Burkly LC, Daemen MJ. Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype. Proc Natl Acad Sci USA 2000;97:7464–7469.

    PubMed  CAS  Google Scholar 

  116. Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 1998;394:200–203.

    PubMed  CAS  Google Scholar 

  117. Lutgens E, Gorelik L, Daemen MJ, et al. Requirement for CD154 in the progression of atherosclerosis. Nat Med 1999;5:1313–1316.

    PubMed  CAS  Google Scholar 

  118. Andre P, Prasad KS, Denis CV, et al. CD40L stabilizes arterial thrombi by a beta3 integrin—dependent mechanism. Nat Med 2002;8:247–252.

    PubMed  CAS  Google Scholar 

  119. Nannizzi-Alaimo L, Alves VL, Phillips DR. Inhibitory effects of glycoprotein IIb/IIIa antagonists and aspirin on the release of soluble CD40 ligand during platelet stimulation. Circulation 2003;107:1123–1128.

    PubMed  CAS  Google Scholar 

  120. Lindemann S, Tolley ND, Dixon DA, et al. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 2001;154:485–490.

    PubMed  CAS  Google Scholar 

  121. Lindemann S, Tolley ND, Eyre JR, Kraiss LW, Mahoney TM, Weyrich AS. Integrins regulate the intracellular distribution of eukaryotic initiation factor 4E in platelets. A checkpoint for translational control. J Biol Chem 2001;276:33947–33951.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, St. Vincents University Hospital, Dublin, Ireland

    Martin Quinn MB, BCh, BAO, PhD, MSc

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  1. Martin Quinn MB, BCh, BAO, PhD, MSc
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  1. Department of Cardiology, St. Vincent’s University Hospital, Dublin, Ireland

    Martin Quinn MB BCh BAO, PhD

  2. University College Dublin, Dublin, Ireland

    Desmond Fitzgerald MD, FRCPI, FESC, AAP (Vice President of Research) (Vice President of Research)

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© 2005 Humana Press Inc., Totowa, NJ

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Quinn, M. (2005). Platelet Physiology. In: Quinn, M., Fitzgerald, D. (eds) Platelet Function. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59259-917-2_1

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  • DOI: https://doi.org/10.1007/978-1-59259-917-2_1

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