Download PDF
Thromb Haemost 1994; 72(04): 519-522
DOI: 10.1055/s-0038-1648906
Originla Article
Schattauer GmbH Stuttgart

Amyloid β-Protein Precursor-Rich Platelet Microparticles in Thrombotic Disease

Shosaku Nomura
1   The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
,
Yutaka Komiyama
2   The Department of Clinico-Laboratory Medicine, Kansai Medical University, Osaka, Japan
,
Tetsuya Miyake
1   The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
,
Yasuhiko Miyazaki
1   The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
,
Hirofumi Kido
1   The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
,
Masahiko Suzuki
1   The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
,
Hideo Kagawa
1   The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
,
Mutsumasa Yanabu
1   The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
,
Hakuo Takahashi
2   The Department of Clinico-Laboratory Medicine, Kansai Medical University, Osaka, Japan
,
Shirou Fukuhara
1   The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
› Author Affiliations
Further Information

Publication History

Received 09 March 1994

Accepted after revision 22 June 1994

Publication Date:
06 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

We investigated the association of amyloid β-protein precursor (APP) and platelet derived microparticles in 20 normal controls and 91 patients with various diseases causing a thrombotic tendency. Compared with the controls, the mean percentage of APP-positive microparticles was significantly greater in the patients with cerebral infarction (39.1 ± 17.7%, p <0.001), diabetes (31.1 ± 12.6%, p <0.001), and uremia (30.1 ± 14.7%, p <0.01), but not in those with hypertension (8.2 ±6.3%, p = NS). Sixteen patients with cerebral infarction, 20 with diabetes, and 11 with uremia had microparticles with very high APP levels. In normal controls, 7.2 ± 3.7% of the microparticles were positive for P-selectin, while the percentage in cerebral infarction, diabetes, uremia, and hypertension was respectively 43.5 ± 15.1%, 40.0 ± 12.8%, 31.8 ±12.2%, and 11.6 ±7.3%. There was a significant correlation between P-selectin and APP positivity of microparticles. Our results suggest that microparticle APP may have a regulatory influence on coagulation abnormalities.

 

  • References

  • 1 Ponte P, Gonzalez-DeWhitt P, Schilling J, Miller J, Hsu D, Greenberg B, Davis K, Wallace W, Lieberburg I, Fuller F, Cordell B. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature 1988; 331: 525-527
    CrossrefPubMedGoogle Scholar
  • 2 Tanzi RE, McClatchey AI, Lamperti ED, Villa-Komaroff L, Gusella JF, Neve RL. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer’sdisease. Nature 1988; 331: 528-530
    CrossrefPubMedGoogle Scholar
  • 3 Kitaguchi N, Takahashi Y, Tokushima Y, Shiojiri S, Ito H. Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity. Nature 1988; 331: 530-532
    CrossrefPubMedGoogle Scholar
  • 4 Van Nostrand WE, Wagner SL, Suzuki M, Choi BH, Farrow JS, Geddes JW, Cotman CW, Cunningham DD. Protease nexin-II, a potent anti-chymotrypsin, shows identity toamyloid b-protein precursor. Nature 1989; 341: 546-549
    CrossrefPubMedGoogle Scholar
  • 5 Van Nostrand WE, Schmaier AH, Farrow JS. Cunningham DD. Protease nexin-II (amyloid b-protein precursor): a platelet-granule protein. Science 1990; 248: 745-748
    CrossrefPubMedGoogle Scholar
  • 6 Cole GM, Galasko D, Shapiro IP, Saitoh T. Stimulated platelets release amyloid b-protein precursor. Biochem Biophys Res Comrnun 1990; 170: 288-295
    PubMedGoogle Scholar
  • 7 Smith RP, Higuchi DA, Broze GJ. Platelet coagulation factor Xla-inhibi-tor, a form of Alzheimer amyloid precursor protein. Science 1990 248: 1126-1128
    PubMedGoogle Scholar
  • 8 Stern RA, Trojanowski JQ, Lee VM-Y. Antibodies to the b-amyloid peptide cross-react with conformational epitopes in human fibrinogen subunits from peripheral blood. FEBS Lett 1990; 264: 43-47
    CrossrefPubMedGoogle Scholar
  • 9 Bush AI, Martins RN, Rumble B, Moir R, Fuller S, Milward E, Currie J, Ames D, Weidemann A, Fischer P, Multhaup G, Beyreuther K, Masters CL. The amyloid precursor protein of Alzheimer’s disease is released by human platelets. J Biol Chem 1990; 265: 15977-15983
    PubMedGoogle Scholar
  • 10 Gardella JE, Gorgone GA, Munoz PC, Ghiso J, Frangione B, Gorevic PD. Protein precursor expression in human platelets and a megakaryocyte cell line: possible implication for the origin of cerebral amyloidosis in Alzheimer’s disease. Lab Invest 1992; 67: 303-312
    PubMedGoogle Scholar
  • 11 Smith RP, Groze GJ. Characterization of platelet-releasable forms of b-amyloid precursor proteins: the effect of thrombin. Blood 1992; 80: 2252-2260
    PubMedGoogle Scholar
  • 12 Komiyama Y, Murakami T, Egawa H, Okubo S, Yasunaga K, Murata K. Purification of factor XIa inhibitor from human platelets. Thromb Res 1992; 66: 397-408
    CrossrefPubMedGoogle Scholar
  • 13 George JN, Pickett EB, Saucerman S, McEver RP, Kunicki TJ, Kieffer N, Newman PJ. Platelet surface glycoproteins: studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery. J Clin Invest 1986; 78: 340-348
    CrossrefPubMedGoogle Scholar
  • 14 Sims PJ, Faioni EM, Wiedmer T, Shattil SJ. Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity. J Biol Chem 1988; 263: 18205-18212
    PubMedGoogle Scholar
  • 15 Abrams CS, Ellison N, Budzynski AZ, Shattil SJ. Direct detection of activated platelets and platelet-derived microparticles in humans. Blood 1990; 75: 128-138
    PubMedGoogle Scholar
  • 16 Abrams CS, Shattil SJ. Immunological detection of activated platelets in clinical disorders. Thromb Haemost 1991; 65: 467-473
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Sims PJ, Wiedmer T, Esmon CT, Weiss HJ, Shattil SJ. Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. J Biol Chem 1989; 264: 17049-17057
    PubMedGoogle Scholar
  • 18 Nomura S, Yasunaga K. Influence of platelet-derived microparticles on coagulation in a lung cancer patient receiving chemotherapy. Chest 1993; 103: 979-980
    PubMedGoogle Scholar
  • 19 Nomura S, Shouzu A, Nishikawa M, Kokawa T, Yasunaga K. Significance of platelet-derived microparticles in uremia. Nephron 1993; 63: 485
    CrossrefPubMedGoogle Scholar
  • 20 Kelton JG, Warkentin TE, Hayward DPM, Murphy WG, Moore JC. Calpain activity in patients with thrombotic thrombocytopenic purpura is associated with platelet microparticles. Blood 1992; 80: 2246-2251
    PubMedGoogle Scholar
  • 21 McEver RP, Martin MN. A monoclonal antibody to a membrane glycoprotein binds only toactivated platelets. J Biol Chem 1984; 259: 9799-9804
    PubMedGoogle Scholar
  • 22 Berman CL, Yea EL, Wencel-Drake JD, Furie BC, Ginsburg MH, Furie B. A platelet alpha granule membrane protein that is incorporated into the plasma membrane during activation. Characterization and subcellular localization of PADGEM protein. J Clin Invest 1985; 78: 130-137
    PubMedGoogle Scholar
  • 23 Nomura S, Suzuki M, Kido H, Yamaguchi K, Fukuroi T, Yanabu M, Soga T, Nagata H, Kokawa T, Yasunaga K. Differences between platelet and microparticle glycoprotein IIb/IIIa. Cytometry 1992; 13: 621-629
    CrossrefPubMedGoogle Scholar
  • 24 Ruan C, Du X, Xi X, Castaldi PA, Berndt MC. A murine antiglycoprotein lb complex monoclonal antibody, SZ2,inhibits platelet aggregation induced by both ristocetin and collagen. Blood 1987; 69: 570-577
    PubMedGoogle Scholar
  • 25 Weidemann A, Konig G, Bunke D, Fischer P, Salbaum JM, Masters CL, Beyreuther K. Identification, biogenesis, an localization of precursors of Alzheimer’s disease A4 amyloid protein. Cell 1989; 57: 115-121
    CrossrefPubMedGoogle Scholar
  • 26 Nieuwenhuis HK, Van Oostem JJG, Rozemuller E, van Iwaarden F, Sixma JJ. Studies with a monoclonal antibody against activated platelets: evidence that a secreted MW 53,000 lysosome-like-granule protein is exposed on the surface of activated platelets in the circulation. Blood 1987; 70: 838-845
    PubMedGoogle Scholar
  • 27 Metzelaar MJ, Korteweg J, Sixma JJ, Nieuwenhuis HK. Comparison of platelet membrane markers for the detection of platelet activation in vitro and during platelet storage and cardiopulmonary bypass surgery. J Lab Clin Med 1993; 121: 579-587
    PubMedGoogle Scholar
  • 28 Wu G, Li F, Li P, Ruan C. Detection of plasma alpha-granule membrane protein GMP-140 using radiolabeled monoclonal antibodies in thrombotic diseases. Haemostasis 1993; 23: 121-128
    PubMedGoogle Scholar
  • 29 Kitaguchi N, Takahashi Y, Oishi K, Shiojiri S, Tokushima Y, Utsunomiya T, Ito H. Enzyme specificity of protease inhibitor region in amyloid precursor protein of Alzheimer’s disease: different properties compared with protease nexin I. Biochim Biophys Acta 1990; 1038: 105-113
    CrossrefPubMedGoogle Scholar
  • 30 Schmaier AH, Dahl LD, Rozemuller AJM, Roos RA, Wagner SL, Chung R, van Nostrand WE. Protease nexin-2/amyloid protein precursor - a tight-binding inhibitor of coagulation factor IXa. J Clin Invest 1993; 92: 2540-2545
    CrossrefPubMedGoogle Scholar
  • 31 Saitoh T, Sundsmo M, Roch JM, Kumura N, Cole G, Schubert D, Olters-dorf T, Schenk DB. Secreted form of amyloid protein precursor is involved in the growth regulation of fibroblasts. Cell 1989; 58: 615-622
    CrossrefPubMedGoogle Scholar