The Interaction of Botrocetin with Normal or Variant von Willebrand Factor (Types IIA and IIB) and Its Inhibition by Monoclonal Antibodies that Block Receptor Binding

Fujimura, Yoshihiro; Miyata, Shigeki; Nishida, Sachiyo; Miura, S.; Kaneda, Mizuho; Yoshioka, Akira; Fukui, Hiromu; Katayama, Masahiko; Tuddenham, Edward G. D.; Usami, Yoshiko

doi:10.1055/s-0038-1646298

Cited by 17 publications

(6 citation statements)

References 16 publications

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“…We have demonstrated that an anti-vWF monoclonal antibody, NMC4, and an anti-GPIb monoclonal antibody, AP-1, inhibit both botrocetin-and ristocetin-induced vWF binding to GPIb (30,31). Our recent results (32) indicate that NMC-4 blocks formation of an activated complex between vWF and two-chain botrocetin, supporting the previous observation that botrocetin binds solely to vWF and not to GPIb (13,14). Furthermore, neither of two synthetic peptides corresponding to two noncontiguous sequences in the constituent subunits of vWF, Cys-474 to Pro-488 and Leu-694 to Pro-708, which were identified as the ristocetin-dependent GPIb binding domain (33), blocked botrocetin-induced binding.…”

Section: Discussionmentioning

confidence: 97%

Primary structure of two-chain botrocetin, a von Willebrand factor modulator purified from the venom of Bothrops jararaca.

Usami

Fujimura

Suzuki

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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111

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The complete amino acid sequence and location of the disulfide bonds of two-chain botrocetin, which promotes platelet agglutination in the presence of von Willebrand factor, from venom of the snake Bothrops jararaca are presented. Sequences of the a and .8 subunits were determined by analysis of peptides generated by digestion of the S-pyridylethylated protein with Achromobacter protease I or a-chymotrypsin and by chemical cleavage with cyanogen bromide or 2-(2'-nitrophenylsulfenyl)-3-methyl-3-bromoindolenine. Twochain botrocetin is a heterodimer composed of the a subunit (consisting of 133 amino acid residues) and the ,B subunit (consisting of 125 amino acid residues) held together by a disulfide bond. Seven disulfide bonds link half-cystine residues 2 to 13, 30 to 128, and 103 to 120 of the a subunit; 2 to 13, 30 to 121, and 98 to 113 of the ,B subunit; and 80 of the a subunit to 75 of the /3 subunit. In terms of amino acid sequence and disuffilde bond location, two-chain botrocetin is homologous to echinoidin (a sea urchin lectin) and other C-type (Ca2+-dependent) lectins.

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Section: Discussionmentioning

confidence: 97%

Primary structure of two-chain botrocetin, a von Willebrand factor modulator purified from the venom of Bothrops jararaca.

Usami

Fujimura

Suzuki

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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111

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“…Although agglutination induced with bothrocetin is normal in type 2M and abnormal in type 2A, with ristocetin it is abnormal in both types. 61,62…”

Section: Bothrocetin-induced Agglutinationmentioning

confidence: 99%

Laboratory Diagnosis of Congenital von Willebrand Disease

Budde¹,

Drewke²,

Mainusch³

et al. 2002

Semin Thromb Hemost

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Von Willebrand disease (vWD) is caused by quantitative or qualitative defects, or both, of the von Willebrand factor (vWF), a multimeric high-molecular glycoprotein (GP). Typically, it affects the primary hemostatic system, which is reflected by a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (1) by supporting platelet adhesion to the injured vessel wall under conditions of high shear forces and (2) by its carrier function for factor VIIIc (FVIIIc) in plasma. Because of the complexity of the disease, diagnosis of vWD is one of the most challenging of any coagulation disorder. The stepwise diagnosis of vWD includes patients and family history, screening procedures (bleeding time [BT], filter tests, platelet counts, activated partial thromboplastin time [aPTT]), confirmatory tests (vWF antigen [vWF:Ag], vWF ristocetin cofactor activity [vWF:RCo], vWF collagen-binding [vWF:CB] assay, ristocetin-induced platelet aggregation [RIPA], FVIIIc) and tests for final classification (multimeric analysis, FVIII binding capacity of vWF [vWF:FVIIIB], platelet vWF). In 1999, we classified 303 patients with congenital vWD as type 1 (n = 122), type 2 (n = 171), and type 3 (n = 10). Type 2 was further subdivided into type 2A (n = 126), type 2B (n = 17), type 2M (n = 22), and type 2N (n = 6). Type 2A showed a remarkable heterogeneity, with only 27.8% (n = 36) of the "classic" IIA pattern. The other high-frequency patterns were type IB (25.4% n = 32) and type IIE/F/H-like structural abnormalities (28.6% n = 36). The spectrum was completed with samples from patients with types 2D, 2C, 2C Miami, smeary structures, and other rare subtypes (together 18.9% n = 23).

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“…In contrast to ristocetin, bothrocetin reacts with a broad spectrum of multimeric forms of vWF and induces vWF-dependent platelet agglutination in various animal species. A distinction can be made between types 2A and 2M by using both ristocetin and bothrocetin as inducers of platelet agglutination (92).…”

Section: Bothrocetin-induced Agglutinationmentioning

confidence: 99%

VON WILLEBRAND FACTORANDVON WILLEBRAND DISEASE

Budde¹,

Schneppenheim²

2001

Rev Clin Exp Hematol

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von Willebrand disease (vWD) is caused by quantitative and/or qualitative defects of the von Willebrand factor (vWF), a multimeric high molecular weight glycoprotein. Typically, it affects the primary hemostatic system, which results in a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (i) by initiating platelet adhesion to the injured vessel wall under conditions of high shear forces, and (ii) by its carrier function for factor VIII in plasma. Accumulating knowledge of the different clinical phenotypes and the pathophysiological basis of the disease translated into a classification that differentiated between quantitative and qualitative defects by means of quantitative and functional parameters, and by analyzing the electrophoretic pattern of vWF multimers. The advent of molecular techniques provided the opportunity for conducting genotype-phenotype studies which have recently helped, not only to elucidate or confirm important functions of vWF and its steps in post-translational processing, but also many disease causing defects. Acquired von Willebrand syndrome (avWS) has gained more attention during the recent years. An international registry was published and recommendation by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis in 2000. It concluded that avWS, although not a frequent disease, is nevertheless probably underdiagnosed. This should be addressed in future prospective studies. The aim of treatment is the correction of the impaired hemostatic system of the patient, ideally including the defects of both primary and secondary hemostasis. Desmopressin is the treatment of choice in about 70% of patients, mostly with type 1, while the others merit treatment with concentrates containing vWF.

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The Interaction of Botrocetin with Normal or Variant von Willebrand Factor (Types IIA and IIB) and Its Inhibition by Monoclonal Antibodies that Block Receptor Binding

Cited by 17 publications

References 16 publications

Primary structure of two-chain botrocetin, a von Willebrand factor modulator purified from the venom of Bothrops jararaca.

Primary structure of two-chain botrocetin, a von Willebrand factor modulator purified from the venom of Bothrops jararaca.

Laboratory Diagnosis of Congenital von Willebrand Disease

VON WILLEBRAND FACTORANDVON WILLEBRAND DISEASE

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