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DOI: 10.1055/s-0038-1653807
Platelet Unresponsiveness to Collagen: Involvement of Glycoprotein Ia-IIa (α2β1 Integrin) Deficiency Associated with a Myeloproliferative Disorder
Publikationsverlauf
Received 09. Juni 1994
Accepted after resubmission 21. November 1994
Publikationsdatum:
09. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199503/lookinside/thumbnails/10-1055-s-0038-1653807-1.jpg)
Summary
We studied a 66-year-old man with a myeloproliferative disorder who presented with a prolonged bleeding time and marked thrombocytosis (platelet count, 3,890 × 109/1). There was no past history of a bleeding disorder. The patient had normal coagulation data. His platelets completely lacked collagen-induced platelet aggregation and adhesion, but showed normal responses to other agonists. All family members tested showed normal platelet aggregation with collagen.
Analysis of 125I surface-labeled platelets by two-dimensional SDS gel electrophoresis disclosed absence of the spot corresponding to platelet membrane GPIa (α2) but no other significant deficiencies of major platelet glycoproteins i.e., GPIb, IIb-IIIa, and IV. Immunoisolation studies of the patient’s platelets indicated that neither anti-GPIa nor anti-GPIIa (β1) monoclonal antibody (mAb) isolated any surface membrane proteins corresponding to GPIa. GPVI, a putative collagen receptor, was immunoisolated from the platelets. Indirect immunofluorescence study using flow cytometry confirmed that the patient’s platelets were totally deficient in surface expression of the GPIa-IIa complex (α2β1, integrin). In contrast, phytohemoagglutinin-activated T-lymphocytes from the patient expressed normal concentrations of this complex.
The data suggest that our patient had an acquired deficiency of the platelet GPIa-IIa complex, due to a myeloproliferative disorder, which might account for the absence of responsiveness of his platelet to collagen.
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References
- 1 Baumgartner HR. Platelet interaction with collagen fibrils in flowing blood. I.Reaction of human platelets with a-chymotrypsin-digested subendothelium. Thromb Haemost 1977; 37: 1-16
- 2 Bensusan HB, Koh TL, Henry KG, Murray BA, Culp LA. Evidence that fibronectin is the collagen receptor on platelet membranes. Proc Natl Acad Sci USA 1978; 75: 5864-5868
- 3 Saito Y, Imada T, Takagi J, Kikuchi T, Indada Y. Platelet factor XIII: the collagen receptor. J Biol Chem 1986; 261: 1355-1358
- 4 Santoro SA, Cowan JF. Adsorption of von Willebrand factor by fibrillar collagen - Implications concerning the adhesion of platelets to collagen. Collagen Relat Res 1982; 2: 31-43
- 5 Lahav J, Schwartz MA, Hynes RO. Analysis of platelet adhesion with a radioactive chemical crosslinking reagent: interaction of thrombospondin with fibronectin and collagen. Cell 1982; 31: 253-262
- 6 Kehrel B, Balleisen L, Kokott R, Mesters R, Stenzinger W, Clemetson KJ, van de Loo J. Deficiency of intact thrombospondin and membrane glycoprotein la in platelets with defective collagen-induced aggregation and spontaneous loss of disorder. Blood 1988; 71: 1074-1078
- 7 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: 913-920
- 8 Kunicki TJ, Nugent DJ, Staats SJ, Orchekowski RP, Wayner EA, Carter WG. The human fibroblast class II extracellular matrix receptor mediates platelet adhesion to collagen and is identical to the platelet glycoprotein Ia-IIa complex. J Biol Chem 1988; 263: 4516-4519
- 9 Staatz WD, Rajpara SM, Wayner EA, Carter WG, Santoro SA. The membrane glycoprotein Ia-IIa (VLA-2) complex mediates the Mg2+-dependent adhesion of platelets to collagen. J Cell Biol 1989; 108: 1917-1924
- 10 Saelman EU M, Nieuwenhuis HK, Hese KM, de Groot PG, Heijnen HF G, Sage EH, Williams S, McKeown L, Gralnick HR, Sixma JJ. Platelet adhesion to collagen type I through VIII under conditions of stasis and flow is mediated by GP Ia/IIa (α2 β1-Integrin). Blood 1994; 83: 1244-1250
- 11 Nieuwenhuis HK, Akkerman JW N, Houdijk WP M, Sixma JJ. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature 1985; 318: 470-472
- 12 Nieuwenhuis HK, Sakariassen KS, Houdijk WP M, Nievelstein PF E M, Sixma JJ. Deficiency of platelet membrane glycoprotein Ia associated with a decreased platelet adhesion to subendothelium. A defect in platelet spreading Blood 1986; 68: 692-695
- 13 Deckmyn H, Chew SL, Vermylen J. Lack of platelet response to collagen associated with an autoantibody against glycoprotein Ia: A novel cause of acquired qualitative platelet dysfunction. Thromb Haemost 1990; 64: 74-79
- 14 Shadle PJ, Ginsberg MH, Plow EF, Barondes SH. Platelet-collagen adhesion: inhibition by a monoclonal antibody that binds glycoprotein lib. J Cell Biol 1984; 99: 2056-2060
- 15 Tandon NN, Kralisz U, Jamieson GA. Identification of glycoprotein IV (CD 36) as a primary receptor for platelet-collagen adhesion. J Biol Chem 1989; 264: 7576-7583
- 16 Tandon NN, Kralisz U, Herman J, Ikeda H, Jamieson GA. NAKa-negative platelets lacking GP IV show reduced adhesion to collagen. Thromb Haemost 1991; 65: 1093
- 17 Asch AS, Liu I, Briccetti FM, Barnwell JW, Kwakye-Berko F, Dokun A, Goldberger J, Pernambuco M. Analysis of CD36 binding domains: ligand specificity controlled by dephosphorylation of an ectodomain. Science 1993; 262: 1436-1440
- 18 Kehrel B, Kronenberg A, Rauterberg J, Niesing-Bresch D, Niehues U, Kardoeus J, Schwippert B, Tschöpe D, van de Loo J, Clemetson KJ. Platelets deficient in glycoprotein IIIb aggregate normally to collagen type V. Blood 1993; 82: 3364-3370
- 19 Chiang TM, Jin A, Kang AH. Platelet-collagen interaction : inhibition by a monoclonal antibody raised against collagen receptor. J Immunol 1987; 139: 887-892
- 20 Kotite NJ, Cunningham LW. Specific adsorption of a platelet membrane glycoprotein by human insoluble collagen. J Biol Chem 1986; 261: 8342-8347
- 21 Deckmyn H, Van Houtte E, Vermylen J. Disturbed platelet aggregation to collagen associated with an antibody against an 85- to 90-Kd platelet glycoprotein in a patient with prolonged bleeding time. Blood 1992; 79: 1466-1471
- 22 Sugiyama T, Okuma M, Ushikubi F, Sensaki S, Kanaji K, Uchino H. A novel platelet aggregating factor found in a patient with defective collagen- induced platelet aggregation and autoimmune thrombocytopenia. Blood 1987; 69: 1712-1720
- 23 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: 1440-1445
- 24 Hynes RO. Integrins : a family of cell surface receptors. Cell 1987; 48: 549-554
- 25 Bolin RB, Okumura T, Jamieson GA. Changes in distribution of platelet membrane glycoproteins in patients with myeloproliferative disorders. Am J Hematol 1977; 3: 63-71
- 26 Eche N, Sie P, Caranobe C, Nouvel C, Pris J, Boneu B. Platelets in myeloproliferative disorders. III: Glycoprotein profile in relation to platelet function and platelet density. Scand J Haematol 1981; 26: 123-129
- 27 Clezardin P, McGregor JL, Dechavanne M, Clemetson KJ. Platelet membrane glycoprotein abnormalities in patients with myeloproliferative disorders and secondary thrombocytosis. Brit J Haematol 1985; 60: 331-344
- 28 Berndt MC, Kabral A, Grimsley P, Watson N, Robertson TI, Bradstock KF. An acquired Bemard-Soulier-like platelet defect associated with juvenile myelodysplastic syndrome. Brit J Haematol 1988; 68: 97-101
- 29 Yufu Y, Hashimoto M, Muta K, Ideguchi H, Nishimura J, Nawata H. Abnormality of platelet membrane glycoprotein GP IIb in a myelodysplastic syndrome with 3q inversion presenting with marked dysmegakaryopoiesis. Acta Haematol 1990; 83: 107-110
- 30 Pischel KD, Bluestein HG, Woods Jr VL. Platelet glycoproteins Ia, Ic and IIa are physicochemically indistinguishable from the very late activation antigen adhesion-related proteins of lymphocytes and other cell types. J Clin Invest 1988; 81: 505-513
- 31 Hemler ME, Ware CF, Strominger JL. Characterization of a novel differentiation antigen complex recognized by a monoclonal antibody (A-1A5): unique activation-specific molecular forms on stimulated T cells. J Immunol 1983; 131: 334-340
- 32 Sonnenberg A, Modderman PW, Hogervorst F. Laminin receptor on platelets is the integrin VLA-6. Nature 1988; 336: 487-489
- 33 Lombardo VT, Hodson E, Roberts JR, Kunicki TJ, Zimmerman TS, Ruggeri Z. Independent modulation of von Willebrand factor and fibrinogen binding to the platelet membrane glycoprotein GPIIb-IIIa complex as demonstrated by monoclonal antibody. J Clin Invest 1985; 76: 1950-1958
- 34 Nagai H, Handa M, Kawai Y, Watanabe K, Ikeda Y. Evidence that plasma fibrinogen and platelet membrane GPIIb-IIIa are involved in the adhesion of platelets to an artificial surface exposed to plasma. Thromb Res 1993; 71: 467-477
- 35 Born GV R, Gross MJ. The aggregation of blood platelets. J Physiol 1963; 168: 178-195
- 36 Phillips DR. Effect of trypsin on the exposed polypeptides and glycoproteins in the human platelet membrane. Biochemistry 1972; 11: 4582-4588
- 37 Phillips DR, Poh-Agin P. Platelet plasma membrane glycoproteins. Evidence for the presence of nonequivalent disulfide bonds using nonreduced-reduced two dimensional gel electrophoresis J Biol Chem 1977; 252: 2121-2126
- 38 O'Farrell PH. High resolution two-dimensional electrophoresis of proteins. J Biol Chem 1975; 250: 4007-4021
- 39 Tamura GS, Dailey MO, Gallatin M, McGrath MS, Weissman IL, Pillemer EA. Isolation of molecules recognized by monoclonal antibodies and anti-sera: the solid phase immunoisolation technique. Anal Biochem 1984; 136: 458-464
- 40 Handa M, Titani K, Holland LZ, Roberts JR, Ruggeri ZM. The von-Wille- brand factor-binding domain of platelet membrane glycoprotein lb. J Biol Chem 1986; 261: 12579-12585
- 41 Kawai Y, Montgomery RR. Endothelial cell processing of von Willebrand proteins. Ann NY Acad Sei 1987; 509: 60-70
- 42 Clemetson KJ. Glycoproteins of the platelet plasma membrane. In: Platelet Membrane Glycoproteins. George JN, Nurden AT, Phillips DR. eds New York: Plenum Press; 1985: 51-85
- 43 Hemler ME, Crouse C, Takata Y, Sonnenberg A. Multiple very late antigen (VLA) heterodimers on platelets. J Biol Chem 1988; 263: 7660-7665
- 44 Parmentier S, Kaplan C, Catimel B, McGregor JL. New families of adhesion molecules play a vital role in platelet functions. Immunology Today 1990; 11: 225-227
- 45 Piotrowicz RS, Orchekowski RP, Nugent DJ, Yamada KY, Kunicki TJ. Glycoprotein Ic-IIa functions as an activation-independent fibronectin receptor on human platelets. J Cell Biol 1988; 106: 1359-1365
- 46 Kunicki TJ, Orchekowski R, Annis D, Honda Y. Variability of integrin α2β2 activity on human platelets. Blood 1993; 82: 2693-2703