GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding

Wolfgang Bergmeier; Tamer Rabie; Amrei Strehl; Crystal L. Piffath; Miroslava Prostredna; Denisa D. Wagner; Bernhard Nieswandt

doi:10.1160/TH03-12-0795

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(05): 951-958
DOI: 10.1160/TH03-12-0795

Platelets and Blood Cells

Schattauer GmbH

GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding

Wolfgang Bergmeier^*

¹The Center for Blood Research, Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts, USA

²Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA

,

Tamer Rabie^*

³Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany

,

Amrei Strehl

³Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany

,

Crystal L. Piffath

¹The Center for Blood Research, Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts, USA

,

Miroslava Prostredna

³Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany

,

Denisa D. Wagner

¹The Center for Blood Research, Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts, USA

²Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA

,

Bernhard Nieswandt

³Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany

› Author Affiliations

Abstract

Summary

Platelet interaction with subendothelial collagen is crucial for hemostasis and thrombosis. Under conditions of elevated shear, platelet adhesion and activation on collagen requires the coordinated action of glycoprotein (GP) Ib and GPVI, which may be physically and functionally linked in the platelet membrane. While the surface expression of GPIb can be down-regulated by internalization and/or proteolytic cleavage of a 130 kDa fragment of GPIbα (glycocalicin, GC), very little is known about the cellular regulation of GPVI. We have recently shown that GPIb on platelets is cleaved by metalloproteinase-dependent mechanisms in response to mitochondrial injury. In the current study, we examined a possible role of platelet metalloproteinases in the regulation of GPVI. Mitochondrial injury induced by incubation of mouse platelets with carbonyl cyanide m-chlorophenyl-hydrazone (CCCP) severely affected the cells´ responses to collagen or the GPVI-specific agonist, collagen related peptide (CRP), but not to thrombin or the stable thromboxane A2 analog U46619.This defect was due to a rapid proteolytic cleavage of GPVI, as shown by the release of the 55 kDa extracellular domain into the supernatant. Both the proteolysis of GPVI and the loss of its activity were inhibited in the presence of the broad range metalloproteinase inhibitor, GM6001. Platelet stimulation with thrombin or CRP, however, resulted in marked metalloproteinase-dependent shedding of GPIbα, but not GPVI suggesting that different metalloproteinases are involved in the regulation of the two receptors or, alternatively, an additional signal is required to render GPVI susceptible to cleavage.

Keywords

Collagen - glycoprotein - metalloproteinase - platelet - shedding

Full Text

References

References
1 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.
2 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.
3 Moog S, Mangin P, Lenain N. et al. Platelet glycoprotein V binds to collagen and participates in platelet adhesion and aggregation. Blood 2001; 98: 1038-46.
4 Moroi M, Jung SM, Okuma M. et al. A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. J Clin Invest 1989; 84: 1440-5.
5 Nieswandt B, Brakebusch C, Bergmeier W. et al. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. EMBO J 2001; 20: 2120-30.
6 Clemetson JM, Polgar J, Magnenat E. et al. The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcalphaR and the natural killer receptors. J Biol Chem 1999; 274: 29019-24.
7 Gibbins JM, Okuma M, Farndale R. et al. Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor gamma-chain. FEBS Lett 1997; 413: 255-9.
8 Tsuji M, Ezumi Y, Arai M. et al. A novel association of Fc receptor gamma-chain with glycoprotein VI and their co-expression as a collagen receptor in human platelets. J Biol Chem 1997; 272: 23528-31.
9 Nieswandt B, Bergmeier W, Schulte V. et al. 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.
10 Kato K, Kanaji T, Russell S. et al. The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletion. Blood 2003; 102: 1701-7.
11 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: 2333-41.
12 Nieswandt B, Schulte V, Bergmeier W. et al. Long-term Antithrombotic Protection by In Vivo Depletion of Platelet Glycoprotein VI in Mice. J Exp Med 2001; 193: 459-70.
13 Schulte V, Rabie T, Prostredna M. et al. Targeting of the collagen-binding site on glycoprotein VI is not essential for in vivo depletion of the receptor. Blood 2003; 101: 3948-52.
14 Massberg S, Gawaz M, Gruner S. et al. A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo. J Exp Med 2003; 197: 41-9.
15 Du X, Magnenat E, Wells TN. et al. Alboluxin, a snake C-type lectin from Trimeresurus albolabris venom is a potent platelet agonist acting via GPIb and GPVI. Thromb Haemost 2002; 87: 692-8.
16 Dormann D, Clemetson JM, Navdaev A. et al. Alboaggregin A activates platelets by a mechanism involving glycoprotein VI as well as glycoprotein Ib. Blood 2001; 97: 929-36.
17 Kanaji S, Kanaji T, Furihata K. et al. Convulxin binds to native, human glycoprotein Ibalpha (GPIbalpha). J Biol Chem 2003; 278: 39452-60.
18 Shrimpton CN, Borthakur G, Larrucea S. et al. Localization of the adhesion receptor glycoprotein Ib-IX-V complex to lipid rafts is required for platelet adhesion and activation. J Exp Med 2002; 196: 1057-66.
19 Locke D, Chen H, Liu Y. et al. Lipid rafts orchestrate signaling by the platelet receptor glycoprotein VI. J Biol Chem 2002; 277: 18801-9.
20 Ezumi Y, Kodama K, Uchiyama T. et al. Constitutive and functional association of the platelet collagen receptor glycoprotein VI-Fc receptor gamma-chain complex with membrane rafts. Blood 2002; 99: 3250-55.
21 Wonerow P, Obergfell A, Wilde JI. et al. Differential role of glycolipid-enriched membrane domains in glycoprotein VI- and integrin-mediated phospholipase Cgamma2 regulation in platelets. Biochem J 2002; 364: 755-65.
22 Falati S, Edmead CE, Poole AW. Glycoprotein Ib-V-IX, a Receptor for von Willebrand Factor, Couples Physically and Functionally to the Fc Receptor gamma- Chain, Fyn, and Lyn to Activate Human Platelets. Blood 1999; 94: 1648-56.
23 Bergmeier W, Burger PC, Piffath CL. et al. Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro aged or injured mouse platelets. Blood 2003; 102: 4229-35.
24 Jurasz P, Chung AW, Radomski A. et al. Nonremodeling properties of matrix metalloproteinases: the platelet connection. Circ Res 2002; 90: 1041-3.
25 Bergmeier W, Rackebrandt K, Schroder W. et al. Structural and functional characterization of the mouse von Willebrand factor receptor GPIb-IX with novel monoclonal antibodies. Blood 2000; 95: 886-93.
26 Bergmeier W, Schulte V, Brockhoff G. et al. Flow cytometric detection of activated mouse integrin alphaIIbbeta3 with a novel monoclonal antibody. Cytometry 2002; 48: 80-6.
27 Lu H, Menashi S, Garcia I. et al. Reversibility of thrombin-induced decrease in platelet glycoprotein Ib function. Br J Haematol 1993; 85: 116-23.
28 Michelson AD, Benoit SE, Kroll MH. et al. The activation-induced decrease in the platelet surface expression of the glycoprotein Ib-IX complex is reversible. Blood 1994; 83: 3562-73.
29 Fox JE. Shedding of adhesion receptors from the surface of activated platelets. Blood Coagul Fibrinolysis 1994; 05: 291-304.
30 Klinger MH. The storage lesion of platelets: ultrastructural and functional aspects. Ann Hematol 1996; 73: 103-12.
31 Alberio L, Friese P, Clemetson KJ. et al. Collagen response and glycoprotein VI function decline progressively as canine platelets age in vivo . Thromb Haemost 2002; 88: 510-6.
32 Brown SB, Clarke MC, Magowan L. et al. Constitutive death of platelets leading to scavenger receptor-mediated phagocytosis. A caspase-independent cell clearance program. J Biol Chem 2000; 275: 5987-96.
33 Chen H, Locke D, Liu Y. et al. 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.
34 Joutsi-Korhonen L, Smethurst PA, Rankin A. et al. The low-frequency allele of the platelet collagen signaling receptor glycoprotein VI is associated with reduced functional responses and expression. Blood 2003; 101: 4372-9.
35 Snell DC, Schulte V, Jarvis GE. et al. Differential effects of reduced glycoprotein VI levels on activation of murine platelets by glycoprotein VI ligands. Biochem J 2002; 368: 293-300.
36 Sugiyama T, Okuma M, Ushikubi F. et al. A novel platelet aggregating factor found in a patient with defective collagen-induced platelet aggregation and autoimmune thrombocytopenia. Blood 1987; 69: 1712-20.
37 Takahashi H, Moroi M. Antibody against platelet membrane glycoprotein VI in a patient with systemic lupus erythematosus. Am J Hematol 2001; 67: 262-7.