Adhesive Domains in the Collagen III Fragment α1(III)CB4 that Support α2β1- and von Willebrand Factor-mediated Platelet Adhesion under Flow Conditions

Marilyn W. Verkleij; Martin J.W. IJsseldijk; Glenda J. Heijnen-Snyder; Eric G. Huizinga; Laurence F. Morton; C. Graham Knight; Jan J. Sixma; Philip G. de Groot; Michael J. Barnes

doi:10.1055/s-0037-1614343

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(03): 1137-1144
DOI: 10.1055/s-0037-1614343

Letters to the Editor

Schattauer GmbH

Adhesive Domains in the Collagen III Fragment α1(III)CB4 that Support α2β1- and von Willebrand Factor-mediated Platelet Adhesion under Flow Conditions

Marilyn W. Verkleij

¹From The Postgraduate School of Biomembranes, Department of Haematology, University Hospital Utrecht, Utrecht, The Netherlands

,

Martin J.W. IJsseldijk

¹From The Postgraduate School of Biomembranes, Department of Haematology, University Hospital Utrecht, Utrecht, The Netherlands

,

Glenda J. Heijnen-Snyder

¹From The Postgraduate School of Biomembranes, Department of Haematology, University Hospital Utrecht, Utrecht, The Netherlands

,

Eric G. Huizinga

¹From The Postgraduate School of Biomembranes, Department of Haematology, University Hospital Utrecht, Utrecht, The Netherlands

,

Laurence F. Morton

²Department of Biochemistry, University of Cambridge, Cambridge, UK

,

C. Graham Knight

²Department of Biochemistry, University of Cambridge, Cambridge, UK

,

Jan J. Sixma

¹From The Postgraduate School of Biomembranes, Department of Haematology, University Hospital Utrecht, Utrecht, The Netherlands

,

Philip G. de Groot

¹From The Postgraduate School of Biomembranes, Department of Haematology, University Hospital Utrecht, Utrecht, The Netherlands

,

Michael J. Barnes

²Department of Biochemistry, University of Cambridge, Cambridge, UK

› Author Affiliations

Abstract

Summary

Seven overlapping peptides derived from the bovine α1(III)CB4 fragment of collagen III support static platelet adhesion, and an integrin α2β1-recognition site has been assigned within this fragment to residues 522-528 of the collagen α1(III) chain; (25). In this study we found that two of the peptides, CB4(III)-6 and -7, were able to support platelet adhesion under flow conditions, whereas the other peptides showed either very little (CB4(III)-1 and -4) or no platelet adhesion at all (CB4(III)-2, -3 and -5). Using the recombinant leech anti-platelet protein (rLAPP), known to prevent both α2β1 integrin- and von Willebrand factor (vWF)-binding to collagen, we observed almost complete inhibition of platelet adhesion to peptides CB4(III)-6 and -7. In solidphase binding assays rLAPP bound to CB4(III)-6 and -7 and to CB4(III)-6/7, containing the peptide 6/7 overlap sequence, and not to any other peptide. Our results suggest that the overlap sequence GPP*-GPRGGAGPP*GPEGGK (single-letter amino acid code, P* = hydroxyproline), corresponding to residues 523-540 of the α1(III) collagen chain, contains a binding site for rLAPP. Monoclonal antibodies (MoAbs) directed against the α2 subunit of integrin α2β1 inhibited platelet adhesion to both CB4(III)-6 and -7 by about 50%, showing that the α2β1-recognition site in this locality in α1(III)CB4 detected under static conditions is of sufficient affinity to withstand shear forces. Solid-phase binding studies indicated that vWF binds to CB4(III)-7 and to a lesser extent to CB4(III)-4. Furthermore, rLAPP competed with vWF in binding to CB4(III)-7. Our results indicate that residues 541-558 of the α1(III)-chain may contain one of the critical vWF-binding sites involved in the initial phase of platelet adhesion to collagen III. MoAbs against vWF (A1 and A3 domain) and glycoprotein (GP)Ib confirmed that vWF is involved in adhesion to CB4(III)-7 and showed that vWF is also involved in adhesion to CB4(III)-6 despite the absence of direct binding of vWF to the peptide. The existence of α2β1-, vWF- and rLAPP-binding sites all in close proximity in α1(III)CB4 testifies to the importance of this locus in collagen III for its platelet reactivity.

Full Text

References

References
1 Verkleij MW, Morton LF, Knight CG, de Groot PG, Barnes MJ, Sixma JJ. Simple collagen-like peptides support platelet adhesion under static but not under flow conditions: interaction via α2β1 and von Willebrand factor with specific sequences in native collagen is a requirement to resist shear forces. Blood 1998; 91: 3808-16.
2 Morton LF, Peachey AR, Barnes MJ. Platelet-reactive sites in collagens type I and type III. Evidence for separate adhesion and aggregatory sites. Biochem J 1989; 258: 157-63.
3 Santoro SA, Walsh JJ, Staatz WD, Baranski KJ. Distinct determinants on collagen support α2β1 integrin-mediated platelet adhesion and platelet activation. Cell Regul 1991; 2: 905-13.
4 Kehrel B, Clemetson KJ, Anders O, Steiner M, Knight CG, Farndale RW, Okuma M, Barnes MJ. Glycoprotein VI is a major collagen receptor for platelet activation: it recognizes the platelet-activating quaternary structure of collagen, whereas CD 36, glycoprotein IIb/IIIa, and von Willebrand factor do not. Blood 1998; 91: 491-9.
5 Weiss HJ, Baumgartner HR, Tschopp TB, Turitto VT, Cohen D. Correction by Factor VIII of the impaired platelet adhesion to subendothelium in von Willebrand’s disease. Blood 1978; 51: 267-79.
6 Baumgartner HR, Tschopp TB, Meyer D. Shear rate dependent inhibition of platelet adhesion and aggregation on collagenous surfaces by antibodies to human factor VIII/von Willebrand factor. Br J Haematol 1980; 44: 127-39.
7 Houdijk WPM, Sakariassen KS, Nievelstein PFEM, Sixma JJ. Role of factor VIII-von Willebrand factor and fibronectin in the interaction of platelets in flowing blood with monomeric and fibrillar human collagen types I and III. J Clin Invest 1985; 75: 531-40.
8 Wu YP, van Breugel HHFI, Lankhof H, Wise RJ, Handin RI, de Groot PG, Sixma JJ. Platelet adhesion to multimeric and dimeric von Willebrand factor and to collagen type III preincubated with von Willebrand factor. Arterioscler Thromb Vasc Biol 1996; 16: 611-20.
9 Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand Factor. Cell 1996; 84: 289-97.
10 Sixma JJ, van Zanten GH, Huizinga EG, van der Plas RM, Verkleij M, Wu YP, Gros P, de Groot PG. Platelet adhesion to collagen: an update. Thromb Haemost 1997; 78: 434-8.
11 Santoro SA, Zutter MM. The α2β1 integrin: a collagen receptor on platelets and other cells. Thromb Haemost 1995; 74: 831-21.
12 Nieuwenhuis HK, Akkerman JWN, Houdijk WPM, Sixma JJ. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature 1985; 318: 470-2.
13 Saelman EUM, Nieuwenhuis HK, Hese KM, de Groot PG, Heijnen HFG, Sage EH, Williams S, McKeown L, Gralnick HR, Sixma JJ. Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (α2β1-integrin). Blood 1994; 83: 1244-50.
14 Morton LF, Hargreaves PG, Farndale RW, Young RD, Barnes MJ. Integrin α2β1-independent activation of platelets by simple collagen-like peptides: collagen tertiary (triple-helical) and quaternary (polymeric) structures are sufficient alone for α2β1-independent platelet reactivity. Biochem J 1995; 306: 337-44.
15 Moroi M, Jung SM, Shinmyozu K, Tomiyama Y, Ordinas A, Diaz-Ricart M. Analysis of platelet adhesion to a collagen-coated surface under flow conditions: the involvement of glycoprotein VI in the platelet adhesion. Blood 1996; 88: 2081-92.
16 Morton LF, Fitzsimmons CM, Rauterberg J, Barnes MJ. Platelet-reactive sites in collagen. Collagens I and III possess different aggregatory sites. Biochem J 1987; 248: 483-7.
17 Staatz WD, Walsh JJ, Pexton T, Santoro SA. The α2β1 integrin cell surface receptor binds to the α1(I)CB3 peptide of collagen. J Biol Chem 1990; 265: 4778-81.
18 Zijenah LS, Barnes MJ. Platelet-reactive sites in human collagens I and III. Evidence for cell-recognition sites in collagen unrelated to RGD and like sequences. Thrombos Res 1990; 59: 553-66.
19 Morton LF, Peachey AR, Zijenah LS, Goodall AH, Humphries MJ, Barnes MJ. Conformation-dependent platelet adhesion to collagen involving integrin α2β1-mediated and other mechanisms: multiple α2β1-recognition sites in collagen type I. Biochem J 1994; 299: 791-97.
20 Saelman EUM, Morton LF, Barnes MJ, Gralnick HR, Hese KM, Nieuwenhuis HK, de Groot PG, Sixma JJ. Platelet adhesion to cyanogen-bromide fragments of collagen α1(I) under flow conditions. Blood 1993; 82: 3029-33.
21 Fitzsimmons CM, Cockburn CG, Hornsey V, Prowse CV, Barnes MJ. The interaction of von Willebrand factor (vWF) with collagen: investigation of vWF-binding sites in the collagen molecule. Thromb Haemost 1988; 59: 186-92.
22 Morton LF, McCulloch IY, Barnes MJ. Platelet aggregation by a collagen-like synthetic peptide. Thrombos Res 1993; 72: 367-72.
23 Rao GHR, Fields CG, White JG, Fields GB. Promotion of human platelet adhesion and aggregation by a synthetic, triple-helical “mini-collagen”. J Biol Chem 1994; 269: 13899-903.
24 Fields GB, Prockop DJ. Perspectives on the synthesis and application of triple-helical, collagen-model peptides. Biopolymers 1996; 40: 345-57.
25 Morton LF, Peachey AR, Knight CG, Farndale RW, Barnes MJ. The platelet reactivity of synthetic peptides based on collagen III fragment α1(III)CB4 – Evidence for an integrin α2β1 recognition site involving residues 522-528 of the α1(III) collagen chain. J Biol Chem 1997; 272: 11044-8.
26 Glattauer V, Werkmeister JA, Kirkpatrick A, Ramshaw JAM. Identification of the epitope for a monoclonal antibody that blocks platelet aggregation induced by type III collagen. Biochem J 1997; 323: 45-9.
27 van Zanten GH, Connolly TM, Schiphorst ME, De Graaf S, Slootweg PJ, Sixma JJ. Recombinant leech anti-platelet protein specifically blocks platelet deposition on collagen surfaces under flow conditions. Arterioscler Thromb Vasc Biol 1995; 15: 1424-31.
28 Gralnick HR, McKeown LP, Williams SS, Lawrence JC, Shafer BC, Kramer WS, Hansmann KE, Vail ML, Magruder LE. A murine monoclonal antibody that identifies a 157/130 kDa platelet collagen receptor. Circulation 1988; 78: 308 (abstr.).
29 Coller BS, Beer JH, Scudder LE, Steinberg MH. Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GPIa/IIa and an indirect interaction with platelet GPIIb/IIIa mediated by adhesive proteins. Blood 1989; 74: 182-92.
30 Berndt MC, Du X, Booth WJ. Ristocetin-dependent reconstitution of binding of von Willebrand Factor to purified human platelet membrane glycoprotein Ib-IX complex. Biochemistry 1988; 27: 633-40.
31 Stel HV, Sakariassen KS, Scholte BJ, Veerman ECI, Van der Kwast TH, De Groot PG, Sixma JJ, Van Mourik JA. Characterization of 25 monoclonal antibodies to factor VIII-von Willebrand factor: relationship between ristocetin-induced platelet aggregation and platelet adherence to subendothelium. Blood 1984; 63: 1408-15.
32 van Zanten HG, Saelman EUM, Schut Hese KM, Wu YP, Slootweg PJ, Nieuwenhuis HK, de Groot PG, Sixma JJ. Platelet adhesion to collagen type IV under flow conditions. Blood 1996; 88: 3862-71.
33 Connolly TM, Jacobs JW, Condra C. An inhibitor of collagen-stimulated platelet activation from the salivary glands of the Haementeria officinalis leech, I: identification, isolation, and characterization. J Biol Chem 1992; 267: 6893-8.
34 Keller PM, Schultz LD, Condra C, Karczewski J, Connolly TM. An inhibitor of collagen-stimulated platelet activation from the salivary glands of the Haementeria officinalis leech, II: cloning of the cDNA and expression. J Biol Chem 1992; 267: 6899-904.
35 Sodetz JM, Pizzo SV, McKee PA. Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. J Biol Chem 1977; 252: 5538-46.
36 Zwaginga JJ, Sixma JJ, de Groot PG. Activation of endothelial cells induces platelet thrombus formation on their matrix. Studies of new in vitro thrombosis model with low molecular weight heparin as anticoagulant. Atherosclerosis 1990; 10: 49-61.
37 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.
38 Depraetere H, Wille C, Gansemans Y, Stanssens P, Lauwereys M, De Reys S, Baruch D, Deckman H. The integrin α2β1 (GPIa/IIa)-I-domain inhibits platelet-collagen interaction. Thromb Haemost 1997; 77: 376 (abstr.).
39 Knight CG, Morton LF, Onley DJ, Peachey AR, Messent AJ, Smethurst PA, Tuckwell DS, Farndale RW, Barnes MJ. Identification in collagen type I of an integrin α2β1-binding site containing an essential GER sequence. J Biol Chem 1998; 273: 33287-93.
40 Nakamura T, Jamieson GA, Okuma M, Kambayashi J, Tandon NN. Platelet adhesion to native type I collagen fibrils. Role of GPVI in divalent cation-dependent and -independent adhesion and thromboxane A₂ generation. J Biol Chem 1998; 273: 4338-44.
41 Cruz MA, Yuan H, Lee JR, Wise RJ, Handin RI. Interaction of the von Willebrand factor (vWF) with collagen. Localization of the primary collagen-binding site by analysis of recombinant vWF A domain polypeptides. J Biol Chem 1995; 270: 10822-7.
42 Lankhof H, van Hoeij M, Schiphorst ME, Bracke M, Wu YP, lJsseldijk MJW, Vink T, de Groot PhG, Sixma JJ. A3 domain is essential for interaction of von Willebrand factor with collagen type III. Thromb Haemost 1996; 75: 950-8.
43 Beumer S, Heijnen HFG, IJsseldijk MJW, Orlando E, de Groot PG, Sixma JJ. Platelet adhesion to fibronectin and in flow: the importance of von Willebrand factor and glycoprotein Ib. Blood 1995; 86: 3452-60.
44 Endenburg SC, Hantgan RR, Lindeboom-Blokzijl L, Lankhof H, Jerome WG, Lewis JC, Sixma JJ, de Groot PG. On the role of von Willebrand factor in promoting platelet adhesion to fibrin in flowing blood. Blood 1995; 86: 4158-65.
45 Chiang TM, Rinaldy A, Kang AH. Cloning, characterization, and functional studies of a non-integrin platelet receptor for type I collagen. J Clin Invest 1997; 100: 514-21.