|
|
Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2003-03-0717.
Submitted March 6, 2003
Accepted April 27, 2003
The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletion
Kazunobu Kato, Taisuke Kanaji, Susan Russell, Thomas J Kunicki, Kenichi Furihata, Sachiko Kanaji, Patrizia Marchese, Armin Reininger, Zaverio M Ruggeri, and Jerry Ware*
Molecular and Experimental Medicine, Roon Research Center for Ateriosclerosis and Thrombosis, The Scripps Research Institute, La Jolla, CA, USA
Experimental Medicine, Torrey Pines Institute for Molecular Studies, San Diego, CA, USA
Transfusion Medicine and Hemostaseology, University of Munich, Munich, Germany
* Corresponding author; email: jware{at}scripps.edu.
Platelet interaction with exposed adhesive ligands at sites of vascular injury is required to initiate a normal hemostatic response and may become a pathogenic factor in arterial diseases leading to thrombosis. We report a targeted disruption in a key receptor for collagen-induced platelet activation, glycoprotein (GP) VI. The breeding of mice with heterozygous GP VI alleles produced the expected frequency of wild-type, heterozygous and homozygous genotypes, indicating that these animals had no reproductive problems and normal viability. GP VInull platelets failed to aggregate in response to type I fibrillar collagen or convulxin, a snake venom protein and known platelet agonist of GP VI. Nevertheless, tail bleeding time measurements revealed no severe bleeding tendency as a consequence of GP VI deficiency. Ex vivo platelet thrombus formation on type I collagen fibrils was abolished using blood from either GP VInull or FcR- null animals. Reflection interference contrast microscopy revealed that the lack of thrombus formation by GP VInull platelets could be linked to a defective platelet activation following normal initial tethering to the surface, visualized as lack of spreading and less stable adhesion. These results illustrate the role of GP VI in post-adhesion events leading to the development of platelet thrombi on collagen fibrils.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. A. Schmaier and M. L. Kahn
Platelet integrin signaling: wherefore art thou?
Blood,
September 24, 2009;
114(13):
2571 - 2572.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mazzucato, M. R. Cozzi, M. Battiston, M. Jandrot-Perrus, M. Mongiat, P. Marchese, T. J. Kunicki, Z. M. Ruggeri, and L. De Marco
Distinct spatio-temporal Ca2+ signaling elicited by integrin {alpha}2{beta}1 and glycoprotein VI under flow
Blood,
September 24, 2009;
114(13):
2793 - 2801.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. A. Senis, M. G. Tomlinson, S. Ellison, A. Mazharian, J. Lim, Y. Zhao, K. N. Kornerup, J. M. Auger, S. G. Thomas, T. Dhanjal, et al.
The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis
Blood,
May 14, 2009;
113(20):
4942 - 4954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Rivera, M. L. Lozano, L. Navarro-Nunez, and V. Vicente
Platelet receptors and signaling in the dynamics of thrombus formation
Haematologica,
May 1, 2009;
94(5):
700 - 711.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kato-Takagaki, Y. Mizukoshi, Y. Yoshizawa, D. Akazawa, Y. Torii, K. Ono, R. Tanimura, I. Shimada, and H. Takahashi
Structural and Interaction Analysis of Glycoprotein VI-binding Peptide Selected from a Phage Display Library
J. Biol. Chem.,
April 17, 2009;
284(16):
10720 - 10727.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Wong, Y. Liu, J. Yip, R. Chand, J. L. Wee, L. Oates, B. Nieswandt, A. Reheman, H. Ni, N. Beauchemin, et al.
CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo
Blood,
February 19, 2009;
113(8):
1818 - 1828.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Auger and S. P. Watson
Dynamic Tyrosine Kinase-Regulated Signaling and Actin Polymerisation Mediate Aggregate Stability Under Shear
Arterioscler Thromb Vasc Biol,
August 1, 2008;
28(8):
1499 - 1504.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Varga-Szabo, I. Pleines, and B. Nieswandt
Cell Adhesion Mechanisms in Platelets
Arterioscler Thromb Vasc Biol,
March 1, 2008;
28(3):
403 - 412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Cheli, D. Jensen, P. Marchese, D. Habart, T. Wiltshire, M. Cooke, J. A. Fernandez, J. Ware, Z. M. Ruggeri, and T. J. Kunicki
The Modifier of hemostasis (Mh) locus on chromosome 4 controls in vivo hemostasis of Gp6-/- mice
Blood,
February 1, 2008;
111(3):
1266 - 1273.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ragab, S. Severin, M.-P. Gratacap, E. Aguado, M. Malissen, M. Jandrot-Perrus, B. Malissen, J. Ragab-Thomas, and B. Payrastre
Roles of the C-terminal tyrosine residues of LAT in GPVI-induced platelet activation: insights into the mechanism of PLC{gamma}2 activation
Blood,
October 1, 2007;
110(7):
2466 - 2474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Calvo, F. Tokumasu, O. Marinotti, J.-L. Villeval, J. M. C. Ribeiro, and I. M. B. Francischetti
Aegyptin, a Novel Mosquito Salivary Gland Protein, Specifically Binds to Collagen and Prevents Its Interaction with Platelet Glycoprotein VI, Integrin {alpha}2beta1, and von Willebrand Factor
J. Biol. Chem.,
September 14, 2007;
282(37):
26928 - 26938.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Rabie, D. Varga-Szabo, M. Bender, R. Pozgaj, F. Lanza, T. Saito, S. P. Watson, and B. Nieswandt
Diverging signaling events control the pathway of GPVI down-regulation in vivo
Blood,
July 15, 2007;
110(2):
529 - 535.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. M. Ruggeri and G. L. Mendolicchio
Adhesion Mechanisms in Platelet Function
Circ. Res.,
June 22, 2007;
100(12):
1673 - 1685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Li, S. Lockyer, A. Concepcion, X. Gong, H. Takizawa, M. Guertin, Y. Matsumoto, J. Kambayashi, N. N. Tandon, and Y. Liu
The Fab Fragment of a Novel Anti-GPVI Monoclonal Antibody, OM4, Reduces In Vivo Thrombosis Without Bleeding Risk in Rats
Arterioscler Thromb Vasc Biol,
May 1, 2007;
27(5):
1199 - 1205.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. J.H. Sachs and B. Nieswandt
In Vivo Thrombus Formation in Murine Models
Circ. Res.,
April 13, 2007;
100(7):
979 - 991.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Hughan, C. E. Hughes, O. J.T. McCarty, E. Schweighoffer, I. Soultanova, J. Ware, V. L.J. Tybulewicz, and S. P. Watson
GPVI Potentiation of Platelet Activation by Thrombin and Adhesion Molecules Independent of Src Kinases and Syk
Arterioscler Thromb Vasc Biol,
February 1, 2007;
27(2):
422 - 429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Strassel, C. Nonne, A. Eckly, T. David, C. Leon, M. Freund, J.-P. Cazenave, C. Gachet, and F. Lanza
Decreased Thrombotic Tendency in Mouse Models of the Bernard-Soulier Syndrome
Arterioscler Thromb Vasc Biol,
January 1, 2007;
27(1):
241 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. F. Samaha and M. L. Kahn
Novel Platelet and Vascular Roles for Immunoreceptor Signaling
Arterioscler Thromb Vasc Biol,
December 1, 2006;
26(12):
2588 - 2593.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Schulte, H. P. Reusch, M. Pozgajova, D. Varga-Szabo, C. Gachet, and B. Nieswandt
Two-Phase Antithrombotic Protection After Anti-Glycoprotein VI Treatment in Mice
Arterioscler Thromb Vasc Biol,
July 1, 2006;
26(7):
1640 - 1647.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Mangin, C. L. Yap, C. Nonne, S. A. Sturgeon, I. Goncalves, Y. Yuan, S. M. Schoenwaelder, C. E. Wright, F. Lanza, and S. P. Jackson
Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcR{gamma} deficiency
Blood,
June 1, 2006;
107(11):
4346 - 4353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dubois, L. Panicot-Dubois, G. Merrill-Skoloff, B. Furie, and B. C. Furie
Glycoprotein VI-dependent and -independent pathways of thrombus formation in vivo
Blood,
May 15, 2006;
107(10):
3902 - 3906.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Inoue, K. Suzuki-Inoue, O. J. T. McCarty, M. Moroi, Z. M. Ruggeri, T. J. Kunicki, Y. Ozaki, and S. P. Watson
Laminin stimulates spreading of platelets through integrin {alpha}6beta1-dependent activation of GPVI
Blood,
February 15, 2006;
107(4):
1405 - 1412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Penz, A. J. Reininger, R. Brandl, P. Goyal, T. Rabie, I. Bernlochner, E. Rother, C. Goetz, B. Engelmann, P. A. Smethurst, et al.
Human atheromatous plaques stimulate thrombus formation by activating platelet glycoprotein VI
FASEB J,
June 1, 2005;
19(8):
898 - 909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Nonne, N. Lenain, B. Hechler, P. Mangin, J.-P. Cazenave, C. Gachet, and F. Lanza
Importance of Platelet Phospholipase C{gamma}2 Signaling in Arterial Thrombosis as a Function of Lesion Severity
Arterioscler Thromb Vasc Biol,
June 1, 2005;
25(6):
1293 - 1298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Hughan, Y. Senis, D. Best, A. Thomas, J. Frampton, P. Vyas, and S. P. Watson
Selective impairment of platelet activation to collagen in the absence of GATA1
Blood,
June 1, 2005;
105(11):
4369 - 4376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Kempton, M. Hoffman, H. R. Roberts, and D. M. Monroe
Platelet Heterogeneity: Variation in Coagulation Complexes on Platelet Subpopulations
Arterioscler Thromb Vasc Biol,
April 1, 2005;
25(4):
861 - 866.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gruner, M. Prostredna, M. Koch, Y. Miura, V. Schulte, S. M. Jung, M. Moroi, and B. Nieswandt
Relative antithrombotic effect of soluble GPVI dimer compared with anti-GPVI antibodies in mice
Blood,
February 15, 2005;
105(4):
1492 - 1499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Stephens, Y. Yan, M. Jandrot-Perrus, J.-L. Villeval, K. J. Clemetson, and D. R. Phillips
Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen
Blood,
January 1, 2005;
105(1):
186 - 191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Pearce, Y. A. Senis, D. D. Billadeau, M. Turner, S. P. Watson, and E. Vigorito
Vav1 and Vav3 Have Critical but Redundant Roles in Mediating Platelet Activation by Collagen
J. Biol. Chem.,
December 24, 2004;
279(52):
53955 - 53962.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Sabri, M. Jandrot-Perrus, J. Bertoglio, R. W. Farndale, V. M.-D. Mas, N. Debili, and W. Vainchenker
Differential regulation of actin stress fiber assembly and proplatelet formation by {alpha}2{beta}1 integrin and GPVI in human megakaryocytes
Blood,
November 15, 2004;
104(10):
3117 - 3125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mazzucato, M. R. Cozzi, P. Pradella, Z. M. Ruggeri, and L. De Marco
Distinct roles of ADP receptors in von Willebrand factor-mediated platelet signaling and activation under high flow
Blood,
November 15, 2004;
104(10):
3221 - 3227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. R.-M. Siljander, S. Hamaia, A. R. Peachey, D. A. Slatter, P. A. Smethurst, W. H. Ouwehand, C. G. Knight, and R. W. Farndale
Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens
J. Biol. Chem.,
November 12, 2004;
279(46):
47763 - 47772.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gruner, M. Prostredna, B. Aktas, A. Moers, V. Schulte, T. Krieg, S. Offermanns, B. Eckes, and B. Nieswandt
Anti-Glycoprotein VI Treatment Severely Compromises Hemostasis in Mice With Reduced {alpha}2{beta}1 Levels or Concomitant Aspirin Therapy
Circulation,
November 2, 2004;
110(18):
2946 - 2951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Kunicki, A. B. Federici, D. R. Salomon, J. A. Koziol, S. R. Head, T. S. Mondala, J. D. Chismar, L. Baronciani, M. T. Canciani, and I. R. Peake
An association of candidate gene haplotypes and bleeding severity in von Willebrand disease (VWD) type 1 pedigrees
Blood,
October 15, 2004;
104(8):
2359 - 2367.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Boylan, H. Chen, V. Rathore, C. Paddock, M. Salacz, K. D. Friedman, B. R. Curtis, M. Stapleton, D. K. Newman, M. L. Kahn, et al.
Anti-GPVI-associated ITP: an acquired platelet disorder caused by autoantibody-mediated clearance of the GPVI/FcR{gamma}-chain complex from the human platelet surface
Blood,
September 1, 2004;
104(5):
1350 - 1355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Gibbins
Platelet adhesion signalling and the regulation of thrombus formation
J. Cell Sci.,
July 15, 2004;
117(16):
3415 - 3425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. E. Kuijpers, V. Schulte, C. Oury, T. Lindhout, J. Broers, M. F. Hoylaerts, B. Nieswandt, and J. W. M. Heemskerk
Facilitating roles of murine platelet glycoprotein Ib and {alpha}IIb{beta}3 in phosphatidylserine exposure during vWF-collagen-induced thrombus formation
J. Physiol.,
July 15, 2004;
558(2):
403 - 415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Nurden, M. Jandrot-Perrus, R. Combrie, J. Winckler, V. Arocas, C. Lecut, J.-M. Pasquet, T. J. Kunicki, and A. T. Nurden
Severe deficiency of glycoprotein VI in a patient with gray platelet syndrome
Blood,
July 1, 2004;
104(1):
107 - 114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Kunicki
Of men; why not mice?
Blood,
May 1, 2004;
103(9):
3251 - 3252.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T.-T. Li, S. Larrucea, S. Souza, S. M. Leal, J. A. Lopez, E. M. Rubin, B. Nieswandt, and P. F. Bray
Genetic variation responsible for mouse strain differences in integrin {alpha}2 expression is associated with altered platelet responses to collagen
Blood,
May 1, 2004;
103(9):
3396 - 3402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kasirer-Friede, M. R. Cozzi, M. Mazzucato, L. De Marco, Z. M. Ruggeri, and S. J. Shattil
Signaling through GP Ib-IX-V activates {alpha}IIb{beta}3 independently of other receptors
Blood,
May 1, 2004;
103(9):
3403 - 3411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. R.-M. Siljander, I. C. A. Munnix, P. A. Smethurst, H. Deckmyn, T. Lindhout, W. H. Ouwehand, R. W. Farndale, and J. W. M. Heemskerk
Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood
Blood,
February 15, 2004;
103(4):
1333 - 1341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Smethurst, L. Joutsi-Korhonen, M. N. O'Connor, E. Wilson, N. S. Jennings, S. F. Garner, Y. Zhang, C. G. Knight, T. R. Dafforn, A. Buckle, et al.
Identification of the primary collagen-binding surface on human glycoprotein VI by site-directed mutagenesis and by a blocking phage antibody
Blood,
February 1, 2004;
103(3):
903 - 911.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gruner, M. Prostredna, V. Schulte, T. Krieg, B. Eckes, C. Brakebusch, and B. Nieswandt
Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo
Blood,
December 1, 2003;
102(12):
4021 - 4027.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kanaji, T. Kanaji, K. Furihata, K. Kato, J. L. Ware, and T. J. Kunicki
Convulxin Binds to Native, Human Glycoprotein Ib{alpha}
J. Biol. Chem.,
October 10, 2003;
278(41):
39452 - 39460.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
