Platelet Membrane Glycoproteins: A Historical Review^[*]

Abstract

The search for the components of the platelet surface that mediate platelet adhesion and platelet aggregation began for earnest in the late 1960s when electron microscopy demonstrated the presence of a carbohydrate-rich, negatively charged outer coat that was called the “glycocalyx.” Progressively, electrophoretic procedures were developed that identified the major membrane glycoproteins (GP) that constitute this layer. Studies on inherited disorders of platelets then permitted the designation of the major effectors of platelet function. This began with the discovery in Paris that platelets of patients with Glanzmann thrombasthenia, an inherited disorder of platelet aggregation, lacked two major GP. Subsequent studies established the role for the GPIIb-IIIa complex (now known as integrin α_IIbβ₃) in binding fibrinogen and other adhesive proteins on activated platelets and the formation of the protein bridges that join platelets together in the platelet aggregate. This was quickly followed by the observation that platelets of patients with the Bernard–Soulier syndrome, with macrothrombocytopenia and a distinct disorder of platelet adhesion, lacked the carbohydrate-rich, negatively charged, GPIb. It was shown that GPIb, through its interaction with von Willebrand factor, mediated platelet attachment to injured sites in the vessel wall. What follows is a personal reflection on the studies that were performed in the early pioneering days.

Keywords

platelet - inherited disorder - membrane glycoproteins - Glanzmann thrombasthenia - Bernard–Soulier syndrome

^* This article is dedicated to Professors Jacques Caen and Peter Castaldi. Jacques Caen is the father of studies on inherited disorders of platelets and gave me my chance during my early years in Paris. His knowledge and drive meant that he was always pushing back the boundaries of knowledge. Peter Castaldi was one of the early pioneers of studies on Glanzmann thrombasthenia and provided much encouragement to me during my early years in Paris. I wish them both a long and happy retirement.

• References

• 1 Nurden AT, Phillips DR, George JN. Platelet membrane glycoproteins: historical perspectives. J Thromb Haemost 2006; 4 (1) 3-9
• 2 Nurden AT. Platelet membrane glycoproteins: a look back into the past and a view to the future. Thromb Haemost 2007; 98 (1) 49-54
• 3 French JE. Blood platelets: morphological studies on their properties and life cycle. Br J Haematol 1967; 13 (4) 595-602
• 4 Sheppard BL, French JE. Platelet adhesion in rabbit arteries observed by scanning and transmission electron microscopy. Nature 1970; 225 (5237) 1054-1055
• 5 Behnke O. Electron microscopical observations on the surface coating of human blood platelets. J Ultrastruct Res 1968; 24 (1) 51-69
• 6 Skaer RJ, Emmines JP, Skaer HB. The fine structure of cell contacts in platelet aggregation. J Ultrastruct Res 1979; 69 (1) 28-42
• 7 Marcus AJ, Ullman HL, Safier LB. Studies on human platelet gangliosides. J Clin Invest 1972; 51 (10) 2602-2612
• 8 Pepper DS, Jamieson GA. Studies on glycoproteins. 3. Isolation of sialylglycopeptides from human platelet membranes. Biochemistry 1969; 8 (8) 3362-3369
• 9 Pepper DS, Jamieson GA. Isolation of a macroglycopeptide from human platelets. Biochemistry 1970; 9 (19) 3706-3713
• 10 Nurden AT. Platelet macroglycopeptide. Nature 1974; 251 (5471) 151-153
• 11 MacPherson GG. Synthesis and localization of sulphated mucopolysaccharide in megakaryocytes and platelets of the rat, an analysis by electron-microscope autoradiography. J Cell Sci 1972; 10 (3) 705-717
• 12 Ward JV, Radojewski-Hutt AM, Packham MA, Haslam RJ, Mustard JF. Loss of sulfated proteoglycan from the surface of rabbit platelets during adenosine 5′-diphosphate-induced aggregation. Lab Invest 1976; 35 (4) 337-342
• 13 Nachman RL, Ferris B. Studies on the proteins of human platelet membranes. J Biol Chem 1972; 247 (14) 4468-4475
• 14 Phillips DR. Effect of trypsin on the exposed polypeptides and glycoproteins in the human platelet membrane. Biochemistry 1972; 11 (24) 4582-4588
• 15 Nachman RL, Hubbard A, Ferris B. Iodination of the human platelet membrane. Studies of the major surface glycoprotein. J Biol Chem 1973; 248 (8) 2928-2936
• 16 George JN, Potterf RD, Lewis PC, Sears DA. Studies on platelet plasma membranes. I. Characterization of surface proteins of human platelets labeled with diazotized (125i)-diiodosulfanilic acid. J Lab Clin Med 1976; 88 (2) 232-246
• 17 McGregor JL, Clemetson KJ, James E , et al. Glycoproteins of platelet membranes from Glanzmann's thrombasthenia. A comparison with normal using carbohydrate-specific or protein-specific labelling techniques and high-resolution two-dimensional gel electrophoresis. Eur J Biochem 1981; 116 (2) 379-388
• 18 Phillips DR, Agin PP. Platelet membrane defects in Glanzmann's thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest 1977; 60 (3) 535-545
• 19 Hagen I, Bjerrum OJ, Solum NO. Characterization of human platelet proteins solubilized with Triton X-100 and examined by crossed immunoelectrophoresis. Reference patterns of extracts from whole platelets and isolated membranes. Eur J Biochem 1979; 99 (1) 9-22
• 20 Hagen I, Nurden A, Bjerrum OJ, Solum NO, Caen J. Immunochemical evidence for protein abnormalities in platelets from patients with Glanzmann's thrombasthenia and Bernard-Soulier syndrome. J Clin Invest 1980; 65 (3) 722-731
• 21 Kunicki TJ, Nurden AT, Pidard D, Russell NR, Caen JP. Characterization of human platelet glycoprotein antigens giving rise to individual immunoprecipitates in crossed-immunoelectrophoresis. Blood 1981; 58 (6) 1190-1197
• 22 Kunicki TJ, Pidard D, Rosa JP, Nurden AT. The formation of Ca++-dependent complexes of platelet membrane glycoproteins IIb and IIIa in solution as determined by crossed immunoelectrophoresis. Blood 1981; 58 (2) 268-278
• 23 Nurden AT, Dupuis D, Pidard D, Kieffer N, Kunicki TJ, Cartron JP. Surface modifications in the platelets of a patient with alpha-N-acetyl-D-galactosamine residues, the Tn-syndrome. J Clin Invest 1982; 70 (6) 1281-1291
• 24 Caen JP, Castaldi PA, Leclerc JC , et al. Congenital bleeding disorders with long bleeding time and normal platelet count. I. Glanzmann's thrombasthenia. Am J Med 1966; 41 (1) 4-26
• 25 Born GVR, Cross MJ. Effects of inorganic ions and of plasma proteins on the aggregation of blood platelets by adenosine diphosphate. J Physiol 1964; 170: 397-414
• 26 Mustard JF, Packham MA, Kinlough-Rathbone RL, Perry DW, Regoeczi E. Fibrinogen and ADP-induced platelet aggregation. Blood 1978; 52 (2) 453-466
• 27 Nurden AT, Caen JP. An abnormal platelet glycoprotein pattern in three cases of Glanzmann's thrombasthenia. Br J Haematol 1974; 28 (2) 253-260
• 28 Nurden AT, Caen JP. Specific roles for platelet surface glycoproteins in platelet function. Nature 1975; 255 (5511) 720-722
• 29 Phillips DR, Jenkins CS, Lüscher EF, Larrieu M. Molecular differences of exposed surface proteins on thrombasthenic platelet plasma membranes. Nature 1975; 257 (5527) 599-600
• 30 Shulman S, Karpatkin S. Crossed immunoelectrophoresis of human platelet membranes. Diminished major antigen in Glanzmann's thrombasthenia and Bernard-Soulier syndrome. J Biol Chem 1980; 255 (9) 4320-4327
• 31 Castaldi PA, Caen J. Platelet fibrinogen. J Clin Pathol 1965; 18 (5) 579-585
• 32 Bernard J, Soulier JP. Sur une nouvelle variété de dystrophie thrombocytairehémoŗragipare congénitale. Sem Hop 1948; 24 (Spec. No.) 3217-3223
• 33 Gröttum KA, Solum NO. Congenital thrombocytopenia with giant platelets: a defect in the platelet membrane. Br J Haematol 1969; 16 (3) 277-290
• 34 Bithell TC, Parekh SJ, Strong RR. Platelet-function studies in the Bernard-Soulier syndrome. Ann N Y Acad Sci 1972; 201: 145-160
• 35 Weiss HJ, Tschopp TB, Baumgartner HR, Sussman II, Johnson MM, Egan JJ. Decreased adhesion of giant (Bernard-Soulier) platelets to subendothelium. Further implications on the role of the von Willebrand factor in hemostasis. Am J Med 1974; 57 (6) 920-925
• 36 Jenkins CS, Phillips DR, Clemetson KJ, Meyer D, Larrieu MJ, Lüscher EF. Platelet membrane glycoproteins implicated in ristocetin-induced aggregation. Studies of the proteins on platelets from patients with Bernard-Soulier syndrome and von Willebrand's disease. J Clin Invest 1976; 57 (1) 112-124
• 37 Nurden AT, Dupuis D, Kunicki TJ, Caen JP. Analysis of the glycoprotein and protein composition of Bernard-Soulier platelets by single and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. J Clin Invest 1981; 67 (5) 1431-1440
• 38 Clemetson KJ, McGregor JL, James E, Dechavanne M, Lüscher EF. Characterization of the platelet membrane glycoprotein abnormalities in Bernard-Soulier syndrome and comparison with normal by surface-labeling techniques and high-resolution two-dimensional gel electrophoresis. J Clin Invest 1982; 70 (2) 304-311
• 39 Cartron JP, Nurden AT. Galactosyltransferase and membrane glycoprotein abnormality in human platelets from Tn-syndrome donors. Nature 1979; 282 (5739) 621-623
• 40 Marguerie GA, Plow EF, Edgington TS. Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chem 1979; 254 (12) 5357-5363
• 41 Bennett JS, Vilaire G. Exposure of platelet fibrinogen receptors by ADP and epinephrine. J Clin Invest 1979; 64 (5) 1393-1401
• 42 Ginsberg MH, Painter RG, Forsyth J, Birdwell C, Plow EF. Thrombin increases expression of fibronectin antigen on the platelet surface. Proc Natl Acad Sci U S A 1980; 77 (2) 1049-1053
• 43 Plow EF, Srouji AH, Meyer D, Marguerie G, Ginsberg MH. Evidence that three adhesive proteins interact with a common recognition site on activated platelets. J Biol Chem 1984; 259 (9) 5388-5391
• 44 Coller BS, Peerschke EI, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest 1983; 72 (1) 325-338
• 45 Pidard D, Montgomery RR, Bennett JS, Kunicki TJ. Interaction of AP-2, a monoclonal antibody specific for the human platelet glycoprotein IIb-IIIa complex, with intact platelets. J Biol Chem 1983; 258 (20) 12582-12586
• 46 Gartner TK, Williams DC, Minion FC, Phillips DR. Thrombin-induced platelet aggregation is mediated by a platelet plasma membrane-bound lectin. Science 1978; 200 (4347) 1281-1283
• 47 Phillips DR, Jennings LK, Edwards HH. Identification of membrane proteins mediating the interaction of human platelets. J Cell Biol 1980; 86 (1) 77-86
• 48 Hoyer LW. Von Willebrand's disease. Prog Hemost Thromb 1976; 3: 231-287
• 49 Ruggeri ZM, Zimmerman TS. Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65 (6) 1318-1325
• 50 Gralnick HR, Williams SB, Morisato DK. Effect of multimeric structure of the factor VIII/von Willebrand factor protein on binding to platelets. Blood 1981; 58 (2) 387-397
• 51 Ruggeri ZM, De Marco L, Gatti L, Bader R, Montgomery RR. Platelets have more than one binding site for von Willebrand factor. J Clin Invest 1983; 72 (1) 1-12
• 52 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 (1) 127-139
• 53 Coller BS, Peerschke EI, Scudder LE, Sullivan CA. Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor. Blood 1983; 61 (1) 99-110
• 54 Ruan C, Tobelem G, McMichael AJ , et al. Monoclonal antibody to human platelet glycoprotein I. II. Effects on human platelet function. Br J Haematol 1981; 49 (4) 511-519
• 55 George JN, Nurden AT, Phillips DR. Molecular defects in interactions of platelets with the vessel wall. N Engl J Med 1984; 311 (17) 1084-1098
• 56 Coller BS, Shattil SJ. The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood 2008; 112 (8) 3011-3025
• 57 Bledzka K, Smyth SS, Plow EF. Integrin αIIbβ3: from discovery to efficacious therapeutic target. Circ Res 2013; 112 (8) 1189-1200
• 58 Vanhoorelbeke K, Ulrichts H, Van de Walle G, Fontayne A, Deckmyn H. Inhibition of platelet glycoprotein Ib and its antithrombotic potential. Curr Pharm Des 2007; 13 (26) 2684-2697
• 59 Hollopeter G, Jantzen HM, Vincent D , et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001; 409 (6817) 202-207
• 60 Michelson AD. Antiplatelet therapies for the treatment of cardiovascular disease. Nat Rev Drug Discov 2010; 9 (2) 154-169
• 61 Nieswandt B, Pleines I, Bender M. Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke. J Thromb Haemost 2011; 9 (Suppl. 01) 92-104
• 62 Brass LF, Wannemacher KM, Ma P, Stalker TJ. Regulating thrombus growth and stability to achieve an optimal response to injury. J Thromb Haemost 2011; 9 (Suppl. 01) 66-75
• 63 Jackson SP. Arterial thrombosis—insidious, unpredictable and deadly. Nat Med 2011; 17 (11) 1423-1436
• 64 Deppermann C, Cherpokova D, Nurden P , et al. Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice. J Clin Invest 2013;