Role of the glycoprotein Ib-binding A1 repeat and the RGD sequence in platelet adhesion to human recombinant von Willebrand factor

Lankhof, H.; Wu, Yaping; Vink, Tom; Schiphorst, Marion E.; Zerwes, Hans‐Günter; Groot, Philip G. de; Sixma, JJ

doi:10.1182/blood.v86.3.1035.1035

Cited by 75 publications

(42 citation statements)

References 36 publications

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“…The results showed vWF undergoes a globular to extended chain conformational transition on a hydrophobic surface in the shear stress regime of 35 + 3.5 dyn/cm 2 . This corresponds to a wall shear rate in blood of ~1,000 s -1 , similar to the range of shear that vWF predominates over fibrinogen as the principal mediator of platelet adhesion [90]. These data are presented in (Fig.…”

Section: Von Willebrand Factor (Vwf)mentioning

confidence: 57%

Molecular Views and Measurements of Hemostatic Processes Using Atomic Force Microscopy

Marchant

Kang

Sit

et al. 2002

curr protein pept sci

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Hemostasis and thrombosis are highly complex and coordinated interfacial responses to vascular injury. In recent years, atomic force microscopy (AFM) has proven to be a very useful approach for studying hemostatic processes under near physiologic conditions. In this report, we review recent progress in the use of AFM for studying hemostatic processes, including molecular level visualization of plasma proteins, protein aggregation and multimer assembly, and structural and morphological details of vascular cells under aqueous conditions. AFM offers opportunities for visualizing surface-dependent molecular and cellular interactions in three dimensions on a nanoscale and for sensitive, picoNewton level, measurements of intermolecular forces. AFM has been used to obtain molecular and sub-molecular, resolution of many biological molecules and assemblies, including coagulation proteins and cell surfaces. Surface-dependent molecular processes including protein adsorption, conformational changes, and subsequent interactions with cellular components have been described. This review outlines the basic principles and utility of AFM for imaging and force measurements, and offers objective perspectives on both the advantages and disadvantages. We focus primarily on molecular level events related to hemostasis and thrombosis, particularly coagulation proteins, and blood platelets, but also explore the use of AFM in force measurements and surface property mapping.

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Section: Von Willebrand Factor (Vwf)mentioning

confidence: 57%

Molecular Views and Measurements of Hemostatic Processes Using Atomic Force Microscopy

Marchant

Kang

Sit

et al. 2002

curr protein pept sci

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“…Results showed that this mAb was able to completely block CHO‐αIIbβ3 cell adhesion and spreading on VWF (Fig 2). This was confirmed by showing that DTT‐treated CHO‐αIIbβ3 cells were unable to adhere and spread on rVWF‐RGGS (data not shown), reported as unable to bind to thrombin‐stimulated platelets (Lankhof et al , 1995).…”

Section: Inhibition Of Dtt‐stimulated Cho‐αiibβ3 Cell Adhesion and Spmentioning

confidence: 68%

Activation of integrin αIIbβ3 expressed in Chinese hamster ovary cells is required for interaction with solid‐phase von Willebrand factor

Mekrache¹,

Legendre²,

Kieffer³

et al. 2002

Br J Haematol

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Summary. Dithiothreitol (DTT) is known to induce an active conformation of aIIbb3 integrin and to promote the aggregation of Chinese hamster ovary (CHO)-aIIbb3 cells in the presence of soluble fibrinogen (Fg). The aim of this study was to compare adhesion and spreading with Fg or von Willebrand factor (VWF) of CHO-aIIbb3 cells in the presence or absence of DTT. Our results indicate that DTT treatment was required to induce cell spreading on VWF. In contrast, CHO-aIIbb3 cell spreading on Fg was already optimal in the absence of DTT. We used a small perfusion chamber coupled to videomicroscopy to demonstrate that CHO-aIIbb3 cells that were adherent and spread on VWF required DTT activation to resist to detachment under increasing shear rates (50-1600/s). In contrast, untreated or DTT-treated cells spread on Fg were able to resist to extremely high flow rates. These data provide novel evidence that activated aIIbb3 is absolutely required for spread cells to resist detachment and strengthens the importance of the aIIbb3 activation step for adhesion and spreading to VWF.

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“…These recombinant variants were used to analyze ADAMTS‐13‐mediated proteolysis. Plasmids pNUT‐VWF encoding wt‐VWF, rVWF/C1130F, rVWF/C1149R and rVWF/C2671Y were stably expressed in baby hamster kidney‐cells overexpressing furin for proper removal of the propeptide [7,18,19]. cDNA encoding wt‐VWF was subcloned into pcDNA6 for co‐transfection to rVWF/C1149R‐expression cells, allowing selection using blasticidin to establish stable cell‐lines expressing heterozygous wt‐VWF‐rVWF/C1149R.…”

Section: Methodsmentioning

confidence: 99%

Cysteine-mutations in von Willebrand factor associated with increased clearance

Schooten

Tjernberg

Westein

et al. 2005

Journal of Thrombosis and Haemostasis

113

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To cite this article: van Schooten CJ, Tjernberg P, Westein E, Terraube V, Castaman G, van Mourik JA, Hollestelle MJ, Vos HL, Bertina RM, van den Berg HM, Eikenboom JCJ, Lenting PJ, Denis CV. Cysteine-mutations in von Willebrand factor associated with increased clearance. J Thromb Haemost 2005; 3: 2228-37.Summary. Background: von Willebrand disease (VWD) is a bleeding disorder caused by the decrease of functional von Willebrand factor (VWF). Low levels of VWF can result from decreased synthesis, impaired secretion, increased clearance or combinations thereof. Several mutations lead to impaired synthesis or secretion of VWF, however, little is known about the survival of VWF in the circulation. Objectives: To evaluate the effect of several VWF mutations on VWF clearance. Patients/methods: The effect of three cysteine-mutations (C1130F, C1149R or C2671Y) on the in vivo survival of VWF was studied in patients carrying these mutations and in a VWFdeficient mice model. Results: In patients carrying these mutations, we observed increased propeptide/mature VWF ratios and rapid disappearance of VWF from the circulation after desmopressin treatment. Detailed analysis of in vivo clearance of recombinant VWF in a VWF-deficient mice model revealed a fourfold increased clearance rate of the mutants. The mutations C1130F, C1149R and C2671Y are each associated with reduced survival of VWF in the circulation. Detailed analysis of the recombinant mutant VWF demonstrated that increased clearance was not due to increased proteolysis by ADAMTS-13. We did not identify functional or structural characteristics that the mutant proteins have in common and could be associated with the phenomenon of increased clearance. Conclusions: Cysteine-mutations in VWF may result in reduced in vivo survival. The observation that various mutations are associated with increased in vivo clearance may have major implications for the therapeutic strategies that rely on the rise of endogenous VWF after desmopressin administration.

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Role of the glycoprotein Ib-binding A1 repeat and the RGD sequence in platelet adhesion to human recombinant von Willebrand factor

Cited by 75 publications

References 36 publications

Molecular Views and Measurements of Hemostatic Processes Using Atomic Force Microscopy

Molecular Views and Measurements of Hemostatic Processes Using Atomic Force Microscopy

Activation of integrin αIIbβ3 expressed in Chinese hamster ovary cells is required for interaction with solid‐phase von Willebrand factor

Cysteine-mutations in von Willebrand factor associated with increased clearance

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