Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke

Journal of Thrombosis and Haemostasis

Volumn 9, Issue 1 S, 2011, Pages 92-104

  Nieswandt, B ^a   Pleines, I ^a   Bender, M ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

CLEC 2; GPIb; GPVI; Ischaemic stroke; Platelet integrin; Thrombosis

Indexed keywords

ABCIXIMAB; ADAM10 ENDOPEPTIDASE; ADENOSINE DIPHOSPHATE; BLOOD CLOTTING FACTOR 10; GLYCOCALICIN; LAMIFIBAN; PHOSPHOLIPASE D1; PROTEIN TYROSINE KINASE; THROMBOXANE A2; TIROFIBAN; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME; VERY LATE ACTIVATION ANTIGEN 2; VERY LATE ACTIVATION ANTIGEN 5; VERY LATE ACTIVATION ANTIGEN 6; VON WILLEBRAND FACTOR;

ARTERY OCCLUSION; ARTERY THROMBOSIS; BERNARD SOULIER DISEASE; BINDING SITE; BLOOD CLOT LYSIS; BRAIN INFARCTION; BRAIN ISCHEMIA; DOWN REGULATION; EXTRACELLULAR MATRIX; GENE MUTATION; HEMOSTASIS; HUMAN; INTRACELLULAR SIGNALING; LIGAND BINDING; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; REPERFUSION INJURY; REVIEW; THROMBOCYTE ACTIVATION; THROMBOCYTE ADHESION; THROMBOCYTE AGGREGATION; THROMBOEMBOLISM; THROMBOGENESIS; THROMBUS;

EID: 79960649902     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2011.04361.x     Document Type: Review

References (176)

1. Italiano JE Jr, Patel-Hett S, Hartwig JH. Mechanics of proplatelet elaboration. J Thromb Haemost 2007; 5 (Suppl. 1): 18-23.
2. Bender M, Eckly A, Hartwig JH, Elvers M, Pleines I, Gupta S, Krohne G, Jeanclos E, Gohla A, Gurniak C, Gachet C, Witke W, Nieswandt B. ADF/n-cofilin-dependent actin turnover determines platelet formation and sizing. Blood 2010; 116: 1767-75.
3. Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002; 8: 1227-34.
4. Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood 2008; 112: 3555-62.
5. Savage B, Almus-Jacobs F, Ruggeri ZM. Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. Cell 1998; 94: 657-66.
6. Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor? Blood 2003; 102: 449-61.
7. Offermanns S. Activation of platelet function through G protein-coupled receptors. Circ Res 2006; 99: 1293-304.
8. Varga-Szabo D, Braun A, Nieswandt B. Calcium signaling in platelets. J Thromb Haemost 2009; 7: 1057-66.
9. Nieswandt B, Varga-Szabo D, Elvers M. Integrins in platelet activation. J Thromb Haemost 2009; 7 (Suppl. 1): 206-9.
10. Day SM, Reeve JL, Myers DD, Fay WP. Murine thrombosis models. Thromb Haemost 2004; 92: 486-94.
11. Falati S, Gross P, Merrill-Skoloff G, Furie BC, Furie B. Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse. Nat Med 2002; 8: 1175-81.
12. Gruner S, Prostredna M, Aktas B, Moers A, Schulte V, Krieg T, Offermanns S, Eckes B, Nieswandt B. Anti-glycoprotein VI treatment severely compromises hemostasis in mice with reduced alpha2beta1 levels or concomitant aspirin therapy. Circulation 2004; 110: 2946-51.
13. Massberg S, Brand K, Gruner S, Page S, Muller E, Muller I, Bergmeier W, Richter T, Lorenz M, Konrad I, Nieswandt B, Gawaz M. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 2002; 196: 887-96.
14. Konishi H, Katoh Y, Takaya N, Kashiwakura Y, Itoh S, Ra C, Daida H. Platelets activated by collagen through immunoreceptor tyrosine-based activation motif play pivotal role in initiation and generation of neointimal hyperplasia after vascular injury. Circulation 2002; 105: 912-6.
15. Massberg S, Gawaz M, Gruner S, Schulte V, Konrad I, Zohlnhofer D, Heinzmann U, Nieswandt B. A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo. J Exp Med 2003; 197: 41-9.
16. Kikuchi S, Umemura K, Kondo K, Saniabadi AR, Nakashima M. Photochemically induced endothelial injury in the mouse as a screening model for inhibitors of vascular intimal thickening. Arterioscler Thromb Vasc Biol 1998; 18: 1069-78.
17. Matsuno H, Uematsu T, Nagashima S, Nakashima M. Photochemically induced thrombosis model in rat femoral artery and evaluation of effects of heparin and tissue-type plasminogen activator with use of this model. J Pharmacol Methods 1991; 25: 303-17.
18. Denis C, Methia N, Frenette PS, Rayburn H, Ullman-Cullere M, Hynes RO, Wagner DD. A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci U S A 1998; 95: 9524-9.
19. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006; 367: 1747-57.
20. Hughes M, Lip GY. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost 2008; 99: 295-304.
21. del Zoppo GJ. Acute anti-inflammatory approaches to ischemic stroke. Ann N Y Acad Sci 2010; 1207: 143-8.
22. Stoll G, Kleinschnitz C, Nieswandt B. Combating innate inflammation: a new paradigm for acute treatment of stroke? Ann N Y Acad Sci 2010; 1207: 149-54.
23. Braeuninger S, Kleinschnitz C. Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems. Exp Transl Stroke Med 2009; 1: 8.
24. Fox JE, Aggerbeck LP, Berndt MC. Structure of the glycoprotein Ib.IX complex from platelet membranes. J Biol Chem 1988; 263: 4882-90.
25. Nurden AT, Didry D, Rosa JP. Molecular defects of platelets in Bernard-Soulier syndrome. Blood Cells 1983; 9: 333-58.
26. Howard MA, Hutton RA, Hardisty RM. Hereditary giant platelet syndrome: a disorder of a new aspect of platelet function. Br Med J 1973; 2: 586-8.
27. Ware J, Russell S, Ruggeri ZM. Generation and rescue of a murine model of platelet dysfunction: the Bernard-Soulier syndrome. Proc Natl Acad Sci U S A 2000; 97: 2803-8.
28. Kato K, Martinez C, Russell S, Nurden P, Nurden A, Fiering S, Ware J. Genetic deletion of mouse platelet glycoprotein Ibbeta produces a Bernard-Soulier phenotype with increased alpha-granule size. Blood 2004; 104: 2339-44.
29. Kahn ML, Diacovo TG, Bainton DF, Lanza F, Trejo J, Coughlin SR. Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and Do not exhibit a Bernard-Soulier phenotype. Blood 1999; 94: 4112-21.
30. Gruner S, Prostredna M, Schulte V, Krieg T, Eckes B, Brakebusch C, Nieswandt B. Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo. Blood 2003; 102: 4021-7.
31. Maxwell MJ, Westein E, Nesbitt WS, Giuliano S, Dopheide SM, Jackson SP. Identification of a 2-stage platelet aggregation process mediating shear-dependent thrombus formation. Blood 2007; 109: 566-76.
32. Nesbitt WS, Westein E, Tovar-Lopez FJ, Tolouei E, Mitchell A, Fu J, Carberry J, Fouras A, Jackson SP. A shear gradient-dependent platelet aggregation mechanism drives thrombus formation. Nat Med 2009; 15: 665-73.
33. Ruggeri ZM, Orje JN, Habermann R, Federici AB, Reininger AJ. Activation-independent platelet adhesion and aggregation under elevated shear stress. Blood 2006; 108: 1903-10.
34. Bergmeier W, Piffath CL, Goerge T, Cifuni SM, Ruggeri ZM, Ware J, Wagner DD. The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci U S A 2006; 103: 16900-5.
35. Canobbio I, Balduini C, Torti M. Signalling through the platelet glycoprotein Ib-V-IX complex. Cell Signal 2004; 16: 1329-44.
36. Ozaki Y, Asazuma N, Suzuki-Inoue K, Berndt MC. Platelet GPIb-IX-V-dependent signaling. J Thromb Haemost 2005; 3: 1745-51.
37. Pleines I, Eckly A, Elvers M, Hagedorn I, Eliautou S, Bender M, Wu X, Lanza F, Gachet C, Brakebusch C, Nieswandt B. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. Blood 2010; 115: 3364-73.
38. Elvers M, Stegner D, Hagedorn I, Kleinschnitz C, Braun A, Kuijpers ME, Boesl M, Chen Q, Heemskerk JW, Stoll G, Frohman MA, Nieswandt B. Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1. Sci Signal 2010; 3: ra1.
39. Kanaji T, Russell S, Ware J. Amelioration of the macrothrombocytopenia associated with the murine Bernard-Soulier syndrome. Blood 2002; 100: 2102-7.
40. Konstantinides S, Ware J, Marchese P, Almus-Jacobs F, Loskutoff DJ, Ruggeri ZM. Distinct antithrombotic consequences of platelet glycoprotein Ibalpha and VI deficiency in a mouse model of arterial thrombosis. J Thromb Haemost 2006; 4: 2014-21.
41. Strassel C, Nonne C, Eckly A, David T, Leon C, Freund M, Cazenave JP, Gachet C, Lanza F. Decreased thrombotic tendency in mouse models of the Bernard-Soulier syndrome. Arterioscler Thromb Vasc Biol 2007; 27: 241-7.
42. Cauwenberghs N, Meiring M, Vauterin S, van Wyk V, Lamprecht S, Roodt JP, Novak L, Harsfalvi J, Deckmyn H, Kotze HF. Antithrombotic effect of platelet glycoprotein Ib-blocking monoclonal antibody Fab fragments in nonhuman primates. Arterioscler Thromb Vasc Biol 2000; 20: 1347-53.
43. Wu D, Vanhoorelbeke K, Cauwenberghs N, Meiring M, Depraetere H, Kotze HF, Deckmyn H. Inhibition of the von Willebrand (VWF)-collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons. Blood 2002; 99: 3623-8.
44. Bender M, Hofmann S, Stegner D, Chalaris A, Bosl M, Braun A, Scheller J, Rose-John S, Nieswandt B. Differentially regulated GPVI ectodomain shedding by multiple platelet-expressed proteinases. Blood 2010; 116: 3347-55.
45. Bergmeier W, Piffath CL, Cheng G, Dole VS, Zhang Y, von Andrian UH, Wagner DD. Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates GPIbalpha shedding from platelets in vitro and in vivo. Circ Res 2004; 95: 677-83.
46. Moroi M, Jung SM. Platelet glycoprotein VI: its structure and function. Thromb Res 2004; 114: 221-33.
47. Pleines I, Elvers M, Strehl A, Pozgajova M, Varga-Szabo D, May F, Chrostek-Grashoff A, Brakebusch C, Nieswandt B. Rac1 is essential for phospholipase C-gamma2 activation in platelets. Pflugers Arch 2009; 457: 1173-85.
48. Watson SP, Auger JM, McCarty OJ, Pearce AC. GPVI and integrin alphaIIb beta3 signaling in platelets. J Thromb Haemost 2005; 3: 1752-62.
49. Bergmeier W, Stefanini L. Novel molecules in calcium signaling in platelets. J Thromb Haemost 2009; 7 (Suppl. 1): 187-90.
50. Braun A, Varga-Szabo D, Kleinschnitz C, Pleines I, Bender M, Austinat M, Bosl M, Stoll G, Nieswandt B. Orai1 (CRACM1) is the platelet SOC channel and essential for pathological thrombus formation. Blood 2009; 113: 2056-63.
51. Grosse J, Braun A, Varga-Szabo D, Beyersdorf N, Schneider B, Zeitlmann L, Hanke P, Schropp P, Muhlstedt S, Zorn C, Huber M, Schmittwolf C, Jagla W, Yu P, Kerkau T, Schulze H, Nehls M, Nieswandt B. An EF hand mutation in Stim1 causes premature platelet activation and bleeding in mice. J Clin Invest 2007; 117: 3540-50.
52. Varga-Szabo D, Braun A, Kleinschnitz C, Bender M, Pleines I, Pham M, Renne T, Stoll G, Nieswandt B. The calcium sensor STIM1 is an essential mediator of arterial thrombosis and ischemic brain infarction. J Exp Med 2008; 205: 1583-91.
53. Varga-Szabo D, Authi KS, Braun A, Bender M, Ambily A, Hassock SR, Gudermann T, Dietrich A, Nieswandt B. Store-operated Ca(2+) entry in platelets occurs independently of transient receptor potential (TRP) C1. Pflugers Arch 2008; 457: 377-87.
54. Shattil SJ, Kim C, Ginsberg MH. The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol 2010; 11: 288-300.
55. Inoue O, Suzuki-Inoue K, McCarty OJ, Moroi M, Ruggeri ZM, Kunicki TJ, Ozaki Y, Watson SP. Laminin stimulates spreading of platelets through integrin alpha6beta1-dependent activation of GPVI. Blood 2006; 107: 1405-12.
56. Arthur JF, Dunkley S, Andrews RK. Platelet glycoprotein VI-related clinical defects. Br J Haematol 2007; 139: 363-72.
57. Dumont B, Lasne D, Rothschild C, Bouabdelli M, Ollivier V, Oudin C, Ajzenberg N, Grandchamp B, Jandrot-Perrus M. Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations. Blood 2009; 114: 1900-3.
58. Hermans C, Wittevrongel C, Thys C, Smethurst PA, Van Geet C, Freson K. A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder. J Thromb Haemost 2009; 7: 1356-63.
59. Kato K, Kanaji T, Russell S, Kunicki TJ, Furihata K, Kanaji S, Marchese P, Reininger A, Ruggeri ZM, Ware J. The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletion. Blood 2003; 102: 1701-7.
60. Lockyer S, Okuyama K, Begum S, Le S, Sun B, Watanabe T, Matsumoto Y, Yoshitake M, Kambayashi J, Tandon NN. GPVI-deficient mice lack collagen responses and are protected against experimentally induced pulmonary thromboembolism. Thromb Res 2006; 118: 371-80.
61. Nieswandt B, Bergmeier W, Schulte V, Rackebrandt K, Gessner JE, Zirngibl H. Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcRgamma chain. J Biol Chem 2000; 275: 23998-4002.
62. Nieswandt B, Schulte V, Bergmeier W, Mokhtari-Nejad R, Rackebrandt K, Cazenave JP, Ohlmann P, Gachet C, Zirngibl H. Long-term antithrombotic protection by in vivo depletion of platelet glycoprotein VI in mice. J Exp Med 2001; 193: 459-69.
63. Schulte V, Rabie T, Prostredna M, Aktas B, Gruner S, Nieswandt B. Targeting of the collagen-binding site on glycoprotein VI is not essential for in vivo depletion of the receptor. Blood 2003; 101: 3948-52.
64. Boylan B, Berndt MC, Kahn ML, Newman PJ. Activation-independent, antibody-mediated removal of GPVI from circulating human platelets: development of a novel NOD/SCID mouse model to evaluate the in vivo effectiveness of anti-human platelet agents. Blood 2006; 108: 908-14.
65. Rabie T, Varga-Szabo D, Bender M, Pozgaj R, Lanza F, Saito T, Watson SP, Nieswandt B. Diverging signaling events control the pathway of GPVI down-regulation in vivo. Blood 2007; 110: 529-35.
66. Bergmeier W, Rabie T, Strehl A, Piffath CL, Prostredna M, Wagner DD, Nieswandt B. GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding. Thromb Haemost 2004; 91: 951-8.
67. Al-Tamimi M, Grigoriadis G, Tran H, Paul E, Servadei P, Berndt MC, Gardiner EE, Andrews RK. Coagulation-induced shedding of platelet glycoprotein VI mediated by factor Xa. Blood 2011; 117: 3912-20.
68. Nieswandt B, Heemskerk JW. Dividing VI by X(a). Blood 2011; 117: 3704-5.
69. Nieswandt B, Brakebusch C, Bergmeier W, Schulte V, Bouvard D, Mokhtari-Nejad R, Lindhout T, Heemskerk JW, Zirngibl H, Fassler R. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. EMBO J 2001; 20: 2120-30.
70. Dubois C, Panicot-Dubois L, Merrill-Skoloff G, Furie B, Furie BC. Glycoprotein VI-dependent and -independent pathways of thrombus formation in vivo. Blood 2006; 107: 3902-6.
71. 3-induced thrombosis. J Thromb Haemost 2011, doi: .
72. Eckly A, Hechler B, Freund M, Zerr M, Cazenave JP, Lanza F, Mangin PH, Gachet C. Mechanisms underlying FeCl(3) -induced arterial thrombosis. J Thromb Haemost 2011; 9: 779-89.
73. Mangin P, Yap CL, Nonne C, Sturgeon SA, Goncalves I, Yuan Y, Schoenwaelder SM, Wright CE, Lanza F, Jackson SP. Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcRgamma deficiency. Blood 2006; 107: 4346-53.
74. Dubois C, Panicot-Dubois L, Gainor JF, Furie BC, Furie B. Thrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model. J Clin Invest 2007; 117: 953-60.
75. Hechler B, Nonne C, Eckly A, Magnenat S, Rinckel JY, Denis CV, Freund M, Cazenave JP, Lanza F, Gachet C. Arterial thrombosis: relevance of a model with two levels of severity assessed by histologic, ultrastructural and functional characterization. J Thromb Haemost 2010; 8: 173-84.
76. Kalia N, Auger JM, Atkinson B, Watson SP. Critical role of FcR gamma-chain, LAT, PLCgamma2 and thrombin in arteriolar thrombus formation upon mild, laser-induced endothelial injury in vivo. Microcirculation 2008; 15: 325-35.
77. Matsumoto Y, Takizawa H, Nakama K, Gong X, Yamada Y, Tandon NN, Kambayashi J. Ex vivo evaluation of anti-GPVI antibody in cynomolgus monkeys: dissociation between anti-platelet aggregatory effect and bleeding time. Thromb Haemost 2006; 96: 167-75.
78. Ohlmann P, Hechler B, Ravanat C, Loyau S, Herrenschmidt N, Wanert F, Jandrot-Perrus M, Gachet C. Ex vivo inhibition of thrombus formation by an anti-glycoprotein VI Fab fragment in non-human primates without modification of glycoprotein VI expression. J Thromb Haemost 2008; 6: 1003-11.
79. Colonna M, Samaridis J, Angman L. Molecular characterization of two novel C-type lectin-like receptors, one of which is selectively expressed in human dendritic cells. Eur J Immunol 2000; 30: 697-704.
80. Sobanov Y, Bernreiter A, Derdak S, Mechtcheriakova D, Schweighofer B, Duchler M, Kalthoff F, Hofer E. A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex. Eur J Immunol 2001; 31: 3493-503.
81. Suzuki-Inoue K, Fuller GL, Garcia A, Eble JA, Pohlmann S, Inoue O, Gartner TK, Hughan SC, Pearce AC, Laing GD, Theakston RD, Schweighoffer E, Zitzmann N, Morita T, Tybulewicz VL, Ozaki Y, Watson SP. A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood 2006; 107: 542-9.
82. Chung CH, Peng HC, Huang TF. Aggretin, a C-type lectin protein, induces platelet aggregation via integrin alpha(2)beta(1) and GPIb in a phosphatidylinositol 3-kinase independent pathway. Biochem Biophys Res Commun 2001; 285: 689-95.
83. Navdaev A, Clemetson JM, Polgar J, Kehrel BE, Glauner M, Magnenat E, Wells TN, Clemetson KJ. Aggretin, a heterodimeric C-type lectin from Calloselasma rhodostoma (malayan pit viper), stimulates platelets by binding to alpha 2beta 1 integrin and glycoprotein Ib, activating Syk and phospholipase Cgamma 2, but does not involve the glycoprotein VI/Fc receptor gamma chain collagen receptor. J Biol Chem 2001; 276: 20882-9.
84. Suzuki-Inoue K, Ozaki Y, Kainoh M, Shin Y, Wu Y, Yatomi Y, Ohmori T, Tanaka T, Satoh K, Morita T. Rhodocytin induces platelet aggregation by interacting with glycoprotein Ia/IIa (GPIa/IIa, Integrin alpha 2beta 1). Involvement of GPIa/IIa-associated src and protein tyrosine phosphorylation. J Biol Chem 2001; 276: 1643-52.
85. Bergmeier W, Bouvard D, Eble JA, Mokhtari-Nejad R, Schulte V, Zirngibl H, Brakebusch C, Fassler R, Nieswandt B. Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha. J Biol Chem 2001; 276: 25121-6.
86. Fuller GL, Williams JA, Tomlinson MG, Eble JA, Hanna SL, Pohlmann S, Suzuki-Inoue K, Ozaki Y, Watson SP, Pearce AC. The C-type lectin receptors CLEC-2 and Dectin-1, but not DC-SIGN, signal via a novel YXXL-dependent signaling cascade. J Biol Chem 2007; 282: 12397-409.
87. Hughes CE, Pollitt AY, Mori J, Eble JA, Tomlinson MG, Hartwig JH, O'Callaghan CA, Futterer K, Watson SP. CLEC-2 activates Syk through dimerization. Blood 2010; 115: 2947-55.
88. Watson AA, Christou CM, James JR, Fenton-May AE, Moncayo GE, Mistry AR, Davis SJ, Gilbert RJ, Chakera A, O'Callaghan CA. The platelet receptor CLEC-2 is active as a dimer. Biochemistry 2009; 48: 10988-96.
89. Severin S, Pollitt AY, Navarro-Nunez L, Nash CA, Mourao-Sa D, Eble JA, Senis YA, Watson SP. Syk-dependent phosphorylation of CLEC-2: a novel mechanism of hem-immunoreceptor tyrosine-based activation motif signaling. J Biol Chem 2011; 286: 4107-16.
90. Watson SP, Herbert JM, Pollitt AY. GPVI and CLEC-2 in hemostasis and vascular integrity. J Thromb Haemost 2010; 8: 1456-67.
91. Bertozzi CC, Schmaier AA, Mericko P, Hess PR, Zou Z, Chen M, Chen CY, Xu B, Lu MM, Zhou D, Sebzda E, Santore MT, Merianos DJ, Stadtfeld M, Flake AW, Graf T, Skoda R, Maltzman JS, Koretzky GA, Kahn ML. Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling. Blood 2010; 116: 661-70.
92. Suzuki-Inoue K, Inoue O, Ding G, Nishimura S, Hokamura K, Eto K, Kashiwagi H, Tomiyama Y, Yatomi Y, Umemura K, Shin Y, Hirashima M, Ozaki Y. Essential in vivo roles of the C-type lectin receptor CLEC-2: embryonic/neonatal lethality of CLEC-2-deficient mice by blood/lymphatic misconnections and impaired thrombus formation of CLEC-2-deficient platelets. J Biol Chem 2010; 285: 24494-507.
93. Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T. Syk tyrosine kinase required for mouse viability and B-cell development. Nature 1995; 378: 303-6.
94. Turner M, Mee PJ, Costello PS, Williams O, Price AA, Duddy LP, Furlong MT, Geahlen RL, Tybulewicz VL. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 1995; 378: 298-302.
95. Wang D, Feng J, Wen R, Marine JC, Sangster MY, Parganas E, Hoffmeyer A, Jackson CW, Cleveland JL, Murray PJ, Ihle JN. Phospholipase Cgamma2 is essential in the functions of B cell and several Fc receptors. Immunity 2000; 13: 25-35.
96. Abtahian F, Guerriero A, Sebzda E, Lu MM, Zhou R, Mocsai A, Myers EE, Huang B, Jackson DG, Ferrari VA, Tybulewicz V, Lowell CA, Lepore JJ, Koretzky GA, Kahn ML. Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 2003; 299: 247-51.
97. Fu J, Gerhardt H, McDaniel JM, Xia B, Liu X, Ivanciu L, Ny A, Hermans K, Silasi-Mansat R, McGee S, Nye E, Ju T, Ramirez MI, Carmeliet P, Cummings RD, Lupu F, Xia L. Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice. J Clin Invest 2008; 118: 3725-37.
98. Uhrin P, Zaujec J, Breuss JM, Olcaydu D, Chrenek P, Stockinger H, Fuertbauer E, Moser M, Haiko P, Fassler R, Alitalo K, Binder BR, Kerjaschki D. Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation. Blood 2010; 115: 3997-4005.
99. Bertozzi CC, Hess PR, Kahn ML. Platelets: covert regulators of lymphatic development. Arterioscler Thromb Vasc Biol 2010; 30: 2368-71.
100. O'Callaghan CA. Thrombomodulation via CLEC-2 targeting. Curr Opin Pharmacol 2009; 9: 90-5.
101. May F, Hagedorn I, Pleines I, Bender M, Vogtle T, Eble J, Elvers M, Nieswandt B. CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis. Blood 2009; 114: 3464-72.
102. Xie J, Wu T, Guo L, Ruan Y, Zhou L, Zhu H, Yun X, Hong Y, Jiang J, Wen Y, Gu J. Molecular characterization of two novel isoforms and a soluble form of mouse CLEC-2. Biochem Biophys Res Commun 2008; 371: 180-4.
103. Ruan Y, Guo L, Qiao Y, Hong Y, Zhou L, Sun L, Wang L, Zhu H, Wang L, Yun X, Xie J, Gu J. RACK1 associates with CLEC-2 and promotes its ubiquitin-proteasome degradation. Biochem Biophys Res Commun 2009; 390: 217-22.
104. Hughes CE, Navarro-Nunez L, Finney BA, Mourao-Sa D, Pollitt AY, Watson SP. CLEC-2 is not required for platelet aggregation at arteriolar shear. J Thromb Haemost 2010; 8: 2328-32.
105. Arai M, Yamamoto N, Moroi M, Akamatsu N, Fukutake K, Tanoue K. Platelets with 10% of the normal amount of glycoprotein VI have an impaired response to collagen that results in a mild bleeding tendency. Br J Haematol 1995; 89: 124-30.
106. Boylan B, Chen H, Rathore V, Paddock C, Salacz M, Friedman KD, Curtis BR, Stapleton M, Newman DK, Kahn ML, Newman PJ. Anti-GPVI-associated ITP: an acquired platelet disorder caused by autoantibody-mediated clearance of the GPVI/FcRgamma-chain complex from the human platelet surface. Blood 2004; 104: 1350-5.
107. Moroi M, Jung SM, Okuma M, Shinmyozu K. A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. J Clin Invest 1989; 84: 1440-5.
108. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell 2002; 110: 673-87.
109. Santoro SA. Identification of a 160, 000 dalton platelet membrane protein that mediates the initial divalent cation-dependent adhesion of platelets to collagen. Cell 1986; 46: 913-20.
110. Holtkotter O, Nieswandt B, Smyth N, Muller W, Hafner M, Schulte V, Krieg T, Eckes B. Integrin alpha 2-deficient mice develop normally, are fertile, but display partially defective platelet interaction with collagen. J Biol Chem 2002; 277: 10789-94.
111. Chen H, Locke D, Liu Y, Liu C, Kahn ML. The platelet receptor GPVI mediates both adhesion and signaling responses to collagen in a receptor density-dependent fashion. J Biol Chem 2002; 277: 3011-9.
112. Bennett JS, Chan C, Vilaire G, Mousa SA, DeGrado WF. Agonist-activated alphavbeta3 on platelets and lymphocytes binds to the matrix protein osteopontin. J Biol Chem 1997; 272: 8137-40.
113. Suh TT, Holmback K, Jensen NJ, Daugherty CC, Small K, Simon DI, Potter S, Degen JL. Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice. Genes Dev 1995; 9: 2020-33.
114. Ruggeri ZM, Dent JA, Saldivar E. Contribution of distinct adhesive interactions to platelet aggregation in flowing blood. Blood 1999; 94: 172-8.
115. Nurden AT. Glanzmann thrombasthenia. Orphanet J Rare Dis 2006; 1: 10.
116. Hodivala-Dilke KM, McHugh KP, Tsakiris DA, Rayburn H, Crowley D, Ullman-Cullere M, Ross FP, Coller BS, Teitelbaum S, Hynes RO. Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest 1999; 103: 229-38.
117. Tronik-Le Roux D, Roullot V, Poujol C, Kortulewski T, Nurden P, Marguerie G. Thrombasthenic mice generated by replacement of the integrin alpha(IIb) gene: demonstration that transcriptional activation of this megakaryocytic locus precedes lineage commitment. Blood 2000; 96: 1399-408.
118. Meadows TA, Bhatt DL. Clinical aspects of platelet inhibitors and thrombus formation. Circ Res 2007; 100: 1261-75.
119. Zhang W, Li YS, Nardi MA, Dang S, Yang J, Ji Y, Li Z, Karpatkin S, Wisniewski T. Dissolution of arterial platelet thrombi in vivo with a bifunctional platelet GPIIIa49-66 ligand which specifically targets the platelet thrombus. Blood 2010; 116: 2336-44.
120. Leath CA III, Douglas JT, Curiel DT, Alvarez RD. Single-chain antibodies: a therapeutic modality for cancer gene therapy (review). Int J Oncol 2004; 24: 765-71.
121. Ginsberg MH, Partridge A, Shattil SJ. Integrin regulation. Curr Opin Cell Biol 2005; 17: 509-16.
122. Gong H, Shen B, Flevaris P, Chow C, Lam SC, Voyno-Yasenetskaya TA, Kozasa T, Du X. G protein subunit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin "outside-in" signaling. Science 2010; 327: 340-3.
123. Shattil SJ, Newman PJ. Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood 2004; 104: 1606-15.
124. Tadokoro S, Shattil SJ, Eto K, Tai V, Liddington RC, de Pereda JM, Ginsberg MH, Calderwood DA. Talin binding to integrin beta tails: a final common step in integrin activation. Science 2003; 302: 103-6.
125. Petrich BG, Marchese P, Ruggeri ZM, Spiess S, Weichert RA, Ye F, Tiedt R, Skoda RC, Monkley SJ, Critchley DR, Ginsberg MH. Talin is required for integrin-mediated platelet function in hemostasis and thrombosis. J Exp Med 2007; 204: 3103-11.
126. Moser M, Nieswandt B, Ussar S, Pozgajova M, Fassler R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med 2008; 14: 325-30.
127. Mory A, Feigelson SW, Yarali N, Kilic SS, Bayhan GI, Gershoni-Baruch R, Etzioni A, Alon R. Kindlin-3: a new gene involved in the pathogenesis of LAD-III. Blood 2008; 112: 2591.
128. Malinin NL, Zhang L, Choi J, Ciocea A, Razorenova O, Ma YQ, Podrez EA, Tosi M, Lennon DP, Caplan AI, Shurin SB, Plow EF, Byzova TV. A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nat Med 2009; 15: 313-8.
129. Svensson L, Howarth K, McDowall A, Patzak I, Evans R, Ussar S, Moser M, Metin A, Fried M, Tomlinson I, Hogg N. Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation. Nat Med 2009; 15: 306-12.
130. Chrzanowska-Wodnicka M, Smyth SS, Schoenwaelder SM, Fischer TH, White GC. Rap1b is required for normal platelet function and hemostasis in mice. J Clin Invest 2005; 115: 680-7.
131. Crittenden JR, Bergmeier W, Zhang Y, Piffath CL, Liang Y, Wagner DD, Housman DE, Graybiel AM. CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nat Med 2004; 10: 982-6.
132. Lee HS, Lim CJ, Puzon-McLaughlin W, Shattil SJ, Ginsberg MH. RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences. J Biol Chem 2009; 284: 5119-27.
133. Du X, Saido TC, Tsubuki S, Indig FE, Williams MJ, Ginsberg MH. Calpain cleavage of the cytoplasmic domain of the integrin beta 3 subunit. J Biol Chem 1995; 270: 26146-51.
134. Pfaff M, Du X, Ginsberg MH. Calpain cleavage of integrin beta cytoplasmic domains. FEBS Lett 1999; 460: 17-22.
135. Xi X, Bodnar RJ, Li Z, Lam SC, Du X. Critical roles for the COOH-terminal NITY and RGT sequences of the integrin beta3 cytoplasmic domain in inside-out and outside-in signaling. J Cell Biol 2003; 162: 329-39.
136. Andrews RK, Karunakaran D, Gardiner EE, Berndt MC. Platelet receptor proteolysis: a mechanism for downregulating platelet reactivity. Arterioscler Thromb Vasc Biol 2007; 27: 1511-20.
137. Andre P, Prasad KS, Denis CV, He M, Papalia JM, Hynes RO, Phillips DR, Wagner DD. CD40L stabilizes arterial thrombi by a beta3 integrin - dependent mechanism. Nat Med 2002; 8: 247-52.
138. Nanda N, Andre P, Bao M, Clauser K, Deguzman F, Howie D, Conley PB, Terhorst C, Phillips DR. Platelet aggregation induces platelet aggregate stability via SLAM family receptor signaling. Blood 2005; 106: 3028-34.
139. Angelillo-Scherrer A, de Frutos PG, Aparicio C, Melis E, Savi P, Lupu F, Arnout J, Dewerchin M, Hoylaerts M, Herbert J, Collen D, Dahlback B, Carmeliet P. Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med 2001; 7: 215-21.
140. Zhu L, Bergmeier W, Wu J, Jiang H, Stalker TJ, Cieslak M, Fan R, Boumsell L, Kumanogoh A, Kikutani H, Tamagnone L, Wagner DD, Milla ME, Brass LF. Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc Natl Acad Sci U S A 2007; 104: 1621-6.
141. Prevost N, Woulfe DS, Jiang H, Stalker TJ, Marchese P, Ruggeri ZM, Brass LF. Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets. Proc Natl Acad Sci U S A 2005; 102: 9820-5.
142. Brass LF, Zhu L, Stalker TJ. Novel therapeutic targets at the platelet vascular interface. Arterioscler Thromb Vasc Biol 2008; 28: s43-50.
143. Rivera J, Lozano ML, Navarro-Nunez L, Vicente V. Platelet receptors and signaling in the dynamics of thrombus formation. Haematologica 2009; 94: 700-11.
144. Stalker TJ, Wu J, Morgans A, Traxler EA, Wang L, Chatterjee MS, Lee D, Quertermous T, Hall RA, Hammer DA, Diamond SL, Brass LF. Endothelial cell specific adhesion molecule (ESAM) localizes to platelet-platelet contacts and regulates thrombus formation in vivo. J Thromb Haemost 2009; 7: 1886-96.
145. Falati S, Patil S, Gross PL, Stapleton M, Merrill-Skoloff G, Barrett NE, Pixton KL, Weiler H, Cooley B, Newman DK, Newman PJ, Furie BC, Furie B, Gibbins JM. Platelet PECAM-1 inhibits thrombus formation in vivo. Blood 2006; 107: 535-41.
146. Dhanjal TS, Ross EA, Auger JM, McCarty OJ, Hughes CE, Senis YA, Buckley CD, Watson SP. Minimal regulation of platelet activity by PECAM-1. Platelets 2007; 18: 56-67.
147. Coutts SB, Goyal M. When recanalization does not improve clinical outcomes. Stroke 2009; 40: 2661.
148. del Zoppo GJ. Microvascular changes during cerebral ischemia and reperfusion. Cerebrovasc Brain Metab Rev 1994; 6: 47-96.
149. Lo EH. Experimental models, neurovascular mechanisms and translational issues in stroke research. Br J Pharmacol 2008; 153 (Suppl. 1): S396-405.
150. Hurn PD, Subramanian S, Parker SM, Afentoulis ME, Kaler LJ, Vandenbark AA, Offner H. T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab 2007; 27: 1798-805.
151. Kleinschnitz C, Schwab N, Kraft P, Hagedorn I, Dreykluft A, Schwarz T, Austinat M, Nieswandt B, Wiendl H, Stoll G. Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation. Blood 2010; 115: 3835-42.
152. Kochanek PM, Hallenbeck JM. Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 1992; 23: 1367-79.
153. Kleinschnitz C, Pozgajova M, Pham M, Bendszus M, Nieswandt B, Stoll G. Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation 2007; 115: 2323-30.
154. Stoll G, Kleinschnitz C, Nieswandt B. The role of glycoprotein Ibalpha and von Willebrand factor interaction in stroke development. Hamostaseologie 2010; 30: 136-8.
155. Kleinschnitz C, De Meyer SF, Schwarz T, Austinat M, Vanhoorelbeke K, Nieswandt B, Deckmyn H, Stoll G. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood 2009; 113: 3600-3.
156. Zhao BQ, Chauhan AK, Canault M, Patten IS, Yang JJ, Dockal M, Scheiflinger F, Wagner DD. von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke. Blood 2009; 114: 3329-34.
157. De Meyer SF, Schwarz T, Deckmyn H, Denis CV, Nieswandt B, Stoll G, Vanhoorelbeke K, Kleinschnitz C. Binding of von Willebrand factor to collagen and glycoprotein Ibalpha, but not to glycoprotein IIb/IIIa, contributes to ischemic stroke in mice - brief report. Arterioscler Thromb Vasc Biol 2010; 30: 1949-51.
158. Fujioka M, Hayakawa K, Mishima K, Kunizawa A, Irie K, Higuchi S, Nakano T, Muroi C, Fukushima H, Sugimoto M, Banno F, Kokame K, Miyata T, Fujiwara M, Okuchi K, Nishio K. ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion. Blood 2010; 115: 1650-3.
159. Zhang ZG, Zhang L, Tsang W, Goussev A, Powers C, Ho KL, Morris D, Smyth SS, Coller BS, Chopp M. Dynamic platelet accumulation at the site of the occluded middle cerebral artery and in downstream microvessels is associated with loss of microvascular integrity after embolic middle cerebral artery occlusion. Brain Res 2001; 912: 181-94.
160. Wahl F, Allix M, Plotkine M, Boulu RG. Neurological and behavioral outcomes of focal cerebral ischemia in rats. Stroke 1992; 23: 267-72.
161. Bigalke B, Stellos K, Geisler T, Kremmer E, Seizer P, May AE, Lindemann S, Melms A, Luft A, Gawaz M. Expression of platelet glycoprotein VI is associated with transient ischemic attack and stroke. Eur J Neurol 2010; 17: 111-7.
162. Al-Tamimi M, Gardiner EE, Thom JY, Shen Y, Cooper MN, Hankey GJ, Berndt MC, Baker RI, Andrews RK. Soluble glycoprotein VI is raised in the plasma of patients with acute ischemic stroke. Stroke 2011; 42: 498-500.
163. Berndt MC, Shen Y, Dopheide SM, Gardiner EE, Andrews RK. The vascular biology of the glycoprotein Ib-IX-V complex. Thromb Haemost 2001; 86: 178-88.
164. Soriano SG, Coxon A, Wang YF, Frosch MP, Lipton SA, Hickey PR, Mayadas TN. Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury. Stroke 1999; 30: 134-9.
165. Muller F, Renne T. Novel roles for factor XII-driven plasma contact activation system. Curr Opin Hematol 2008; 15: 516-21.
166. Kleinschnitz C, Stoll G, Bendszus M, Schuh K, Pauer HU, Burfeind P, Renne C, Gailani D, Nieswandt B, Renne T. Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J Exp Med 2006; 203: 513-8.
167. Hagedorn I, Schmidbauer S, Pleines I, Kleinschnitz C, Kronthaler U, Stoll G, Dickneite G, Nieswandt B. Factor XIIa inhibitor recombinant human albumin Infestin-4 abolishes occlusive arterial thrombus formation without affecting bleeding. Circulation 2010; 121: 1510-7.
168. Austinat M, Braeuninger S, Pesquero JB, Brede M, Bader M, Stoll G, Renne T, Kleinschnitz C. Blockade of bradykinin receptor B1 but not bradykinin receptor B2 provides protection from cerebral infarction and brain edema. Stroke 2009; 40: 285-93.
169. Boilard E, Nigrovic PA, Larabee K, Watts GF, Coblyn JS, Weinblatt ME, Massarotti EM, Remold-O'Donnell E, Farndale RW, Ware J, Lee DM. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 2010; 327: 580-3.
170. Muller F, Mutch NJ, Schenk WA, Smith SA, Esterl L, Spronk HM, Schmidbauer S, Gahl WA, Morrissey JH, Renne T. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 2009; 139: 1143-56.
171. Adams HP Jr, Effron MB, Torner J, Davalos A, Frayne J, Teal P, Leclerc J, Oemar B, Padgett L, Barnathan ES, Hacke W. Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II). Stroke 2008; 39: 87-99.
172. Ciccone A, Abraha I, Santilli I. Glycoprotein IIb-IIIa inhibitors for acute ischemic stroke. Stroke 2007; 38: 1113-4.
173. Choudhri TF, Hoh BL, Zerwes HG, Prestigiacomo CJ, Kim SC, Connolly ES Jr, Kottirsch G, Pinsky DJ. Reduced microvascular thrombosis and improved outcome in acute murine stroke by inhibiting GP IIb/IIIa receptor-mediated platelet aggregation. J Clin Invest 1998; 102: 1301-10.
174. Ishikawa M, Cooper D, Arumugam TV, Zhang JH, Nanda A, Granger DN. Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion and reperfusion. J Cereb Blood Flow Metab 2004; 24: 907-15.
175. Abumiya T, Fitridge R, Mazur C, Copeland BR, Koziol JA, Tschopp JF, Pierschbacher MD, del Zoppo GJ. Integrin alpha(IIb)beta(3) inhibitor preserves microvascular patency in experimental acute focal cerebral ischemia. Stroke 2000; 31: 1402-9.
176. Massberg S, Schurzinger K, Lorenz M, Konrad I, Schulz C, Plesnila N, Kennerknecht E, Rudelius M, Sauer S, Braun S, Kremmer E, Emambokus NR, Frampton J, Gawaz M. Platelet adhesion via glycoprotein IIb integrin is critical for atheroprogression and focal cerebral ischemia: an in vivo study in mice lacking glycoprotein IIb. Circulation 2005; 112: 1180-8.