Ristocetin-mediated interaction of human von Willebrand factor with platelet glycoprotein Ib evokes a transient calcium signal: Observations with Fura-PE3

Milner, Elizabeth P.; Zheng, Qiujian; Kermode, John C.

doi:10.1016/s0022-2143(98)90077-4

Cited by 19 publications

(20 citation statements)

References 34 publications

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“…Agonists were added after 65 s of fluorescence recording. For stirred, phosphate-buffered saline (PBS)-treated control platelets, in which aggregation occurred, the measured [Ca 21 ] i values were corrected for the loss of platelet aggregates from the light path using a modified fluorescence cuvette, as described by Milner et al (1998).…”

Section: Methodsmentioning

confidence: 99%

Greater inhibition of platelet procoagulant activity by antibody‐derived glycoprotein IIb–IIIa inhibitors than by peptide and peptidomimetic inhibitors

Lages

Weiss

2001

Br J Haematol

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Summary. Antibody-derived GPIIb±IIIa antagonists, such as the c7E3 Fab fragment abciximab, have been shown to inhibit platelet procoagulant activity as well as platelet aggregation. Whether low-molecular-weight peptide-derived and peptidomimetic antagonists also inhibit platelet procoagulant activity in a similar manner has not been fully investigated. We compared the effects of the antibodyderived antagonists c7E3 Fab and m10E5 IgG, the peptidederived antagonists eptifibatide, MK-852 and RGDS, and the peptidomimetic RO44±9883 on platelet procoagulant activity and on the stimulated cytosolic calcium increases that promote procoagulant activity. Procoagulant activity was measured as prothrombinase activity in gel-filtered platelets, activated by collagen plus thrombin or collagen alone, with and without stirring. The stimulated increases in cytosolic calcium were measured in parallel samples of platelets loaded with fura-2AM. Both c7E3 and m10E5 inhibited prothrombinase activity by 40±50% under all conditions of activation tested and inhibited cytosolic calcium increases to a similar extent in stirred, but not unstirred, platelets. The low-molecular-weight antagonists caused significantly less inhibition of prothrombinase activity in collagen plus thrombin-stimulated platelets, and produced no inhibition but rather a slight enhancement of activity in platelets stimulated by collagen alone. These antagonists also had little or no effect on the cytosolic calcium increases in stirred platelets. These differential effects of antibody-derived versus non-antibody GPIIb±IIIa antagonists on procoagulant activity may be a factor contributing to the differing anti-thrombotic effects of these antagonists seen in clinical trials.

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Section: Methodsmentioning

confidence: 99%

Greater inhibition of platelet procoagulant activity by antibody‐derived glycoprotein IIb–IIIa inhibitors than by peptide and peptidomimetic inhibitors

Lages

Weiss

2001

Br J Haematol

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“…Binding of VWF to GPIb-V-IX upregulates integrin αIIbβ3 affinity (Asazuma et al, 1997;Kasirer-Friede et al, 2004;Milner et al, 1998;Munday et al, 2000;Nesbitt et al, 2002;Torti et al, 1999;Yuan et al, 1999). The integrin can then bind to VWF, thereby enhancing adhesion, and contributing to thrombus formation by binding to fibrinogen.…”

Section: The Gpib-v-ix Complexmentioning

confidence: 99%

“…The binding of VWF to GPIb under shear stress can stimulate calcium mobilization (Kroll et al, 1991;Mazzucato et al, 2002;Milner et al, 1998;Nesbitt et al, 2002;Yap et al, 2000), protein kinase C (PKC), protein kinase G (PKG) (Li et al, 2003;Yap et al, 2000), phosphoinositide 3-kinase (PI3K) (Jackson et al, 1994;Munday et al, 2000;Yap et al, 2000) and cytoskeletal rearrangements (Torti et al, 1999;Yuan et al, 1999). VWF binding also upregulates integrin αIIbβ3 affinity indirectly through the stimulation of ADP secretion (Moake et al, 1988).…”

Section: Signalling Through Gpibmentioning

confidence: 99%

Platelet adhesion signalling and the regulation of thrombus formation

Gibbins

2004

Journal of Cell Science

259

232

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Platelets perform a central role in haemostasis and thrombosis. They adhere to subendothelial collagens exposed at sites of blood vessel injury via the glycoprotein (GP) Ib-V-IX receptor complex, GPVI and integrin α2β1. These receptors perform distinct functions in the regulation of cell signalling involving non-receptor tyrosine kinases (e.g. Src, Fyn, Lyn, Syk and Btk), adaptor proteins, phospholipase C and lipid kinases such as phosphoinositide 3-kinase. They are also coupled to an increase in cytosolic calcium levels and protein kinase C activation, leading to the secretion of paracrine/autocrine platelet factors and an increase in integrin receptor affinities. Through the binding of plasma fibrinogen and von Willebrand Factor to integrin αIIbβ3, a platelet thrombus is formed. Although increasing evidence indicates that each of the adhesion receptors GPIb-V-IX and GPVI and integrins α2β1 and αIIbβ3 contribute to the signalling that regulates this process, the individual roles of each are only beginning to be dissected. By contrast, adhesion receptor signalling through platelet endothelial cell adhesion molecule 1 (PECAM-1) is implicated in the inhibition of platelet function and thrombus formation in the healthy circulation. Recent studies indicate that understanding of platelet adhesion signalling mechanisms might enable the development of new strategies to treat and prevent thrombosis.

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“…Binding of VWF to GPIb under conditions of shear initiates a series of platelet-activating events, including activation of phosphatidylinositol (PI)-3 kinase, 3-5 activation of protein kinases C and G, 6,7 initiation of actin polymerization and cytoskeletal reorganization, 8,9 and elevation of cytosolic calcium 10 derived from intracellular stores. 6, [11][12][13] Although none of the components of the GPIb/V/IX complex possess intrinsic kinase activity, VWF binding to GPIb has nevertheless been shown to cause tyrosine phosphorylation of multiple cytosolic signaling proteins, 3, [14][15][16] activation of which serves to initiate and/or amplify signaling cascades that support formation of stable plateletplatelet and platelet-extracellular matrix interactions. pp60 Src was one of the first proteins found to become tyrosine phosphorylated following engagement of GPIb.…”

Section: Introductionmentioning

confidence: 99%