Characterization of an antiglycoprotein Ib monoclonal antibody that specifically inhibits platelet-thrombin interaction

Мазуров, А. В.; Vinogradov, D. V.; Власик, Т. Н.; Repin, V. S.; Booth, William J.; Berndt, Michael C.

doi:10.1016/0049-3848(91)90371-3

Cited by 49 publications

(35 citation statements)

References 18 publications

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“…On the other hand, VM16d shares the same binding site as aggretin. VM16d is a well characterized monoclonal antibody to GPIb with its epitope in the double-loop region (27) that inhibits thrombinbinding but not von Willebrand factor binding (28) and must therefore bind to one face of the GPIb␣ molecule. These results suggest that the previous studies did not detect aggretin (rhodocytin) binding to GPIb because the anti-GPIb reagents used did not bind to the same region (or face) of GPIb.…”

Section: Discussionmentioning

confidence: 99%

Aggretin, a Heterodimeric C-type Lectin from Calloselasma rhodostoma (Malayan Pit Viper), Stimulates Platelets by Binding to α2β1 Integrin and Glycoprotein Ib, Activating Syk and Phospholipase Cγ2, but Does Not Involve the Glycoprotein VI/Fc Receptor γ Chain Collagen Receptor

Navdaev

Clemetson

Polgár

et al. 2001

Journal of Biological Chemistry

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Aggretin, a potent platelet activator, was isolated from Calloselasma rhodostoma venom, and 30-amino acid N-terminal sequences of both subunits were determined. Aggretin belongs to the heterodimeric snake Ctype lectin family and is thought to activate platelets by binding to platelet glycoprotein ␣ 2 ␤ 1 . We now show that binding to glycoprotein (GP) Ib is also required. Aggretin-induced platelet activation was inhibited by a monoclonal antibody to GPIb as well as by antibodies to ␣ 2 ␤ 1 . Binding of both of these platelet receptors to aggretin was confirmed by affinity chromatography. No binding of other major platelet membrane glycoproteins, in particular GPVI, to aggretin was detected. Aggretin also activates platelets from Fc receptor ␥ chain (Fc␥)-deficient mice to a greater extent than those from normal control mice, showing that it does not use the GPVI/Fc␥ pathway. Platelets from Fc␥-deficient mice expressed fibrinogen receptors normally in response to collagen, although they did not aggregate, indicating that these platelets may partly compensate via other receptors including ␣ 2 ␤ 1 or GPIb for the lack of the Fc␥ pathway. Signaling by aggretin involves a dose-dependent lag phase followed by rapid tyrosine phosphorylation of a number of proteins. Among these are p72 SYK , p125 FAK , and PLC␥2, whereas, in comparison with collagen and convulxin, the Fc␥ subunit neither is phosphorylated nor coprecipitates with p72 SYK . This supports an independent, GPIb-and integrin-based pathway for activation of p72 SYK not involving the Fc␥ receptor.Platelet-collagen interactions are integral to primary hemostasis (1, 2). Resting platelets using several receptors adhering to subendothelium of damaged blood vessels are activated and spread to provide finally a new nonthrombogenic surface until vasculature regeneration occurs. Reversible binding between GPIb-V-IX 1 and von Willebrand factor, associated with collagen, is crucial to slow down the platelet (especially under high shear) so that it can bind more firmly via other receptors (3, 4). This mechanism strongly parallels that of the selectins in leukocyte adhesion (5). Another important receptor is the ␣ 2 ␤ 1 integrin, which is essential for anchoring the platelet to collagen in the subendothelium (6) and for linking to the platelet cytoskeleton to prevent the receptor being torn from the membrane by the forces that it has to withstand. Activation induces the release of storage granules and the expression of new receptors on the platelet surface (7) as well as changes in other receptors such as the fibrinogen receptor, ␣ IIb ␤ 3 , which is critical for spreading. Although GPIb-V-IX and ␣ 2 ␤ 1 also participate in signaling to the platelet interior (8, 9), recent studies, particularly in patients with platelet receptor deficiencies, have implicated GPVI/Fc␥ as a major collagen receptor for platelet activation (10 -12). Patients with platelets lacking any one of these receptors (GPIb-V-IX, ␣ 2 ␤ 1 , or GPVI/Fc␥) have increased bleeding times, and platelet adhesio...

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Section: Discussionmentioning

confidence: 99%

Aggretin, a Heterodimeric C-type Lectin from Calloselasma rhodostoma (Malayan Pit Viper), Stimulates Platelets by Binding to α2β1 Integrin and Glycoprotein Ib, Activating Syk and Phospholipase Cγ2, but Does Not Involve the Glycoprotein VI/Fc Receptor γ Chain Collagen Receptor

Navdaev

Clemetson

Polgár

et al. 2001

Journal of Biological Chemistry

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“…24,25 ; VM16d mAb was kindly provided by Dr Michael Berndt (Monash University, Clayton, Victoria, Australia). 26 …”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Physical proximity and functional interplay of PECAM-1 with the Fc receptor FcγRIIa on the platelet plasma membrane

Thai

Ashman

Harbour

et al. 2003

Blood

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“…[22][23][24] CHO cells stably transfected with GPIb␤ and GPIX (CHO ␤IX cells) were prepared as reported. [25][26][27] Murine monoclonal antibodies AP1 23,28 and VM16d, 20,29 directed against the N-terminal vWF-binding domain of GPIb␣, and WM23, directed against an epitope within the extracellular macroglycopeptide region of GPIb␣, were purified as described in detail elsewhere. 23 Botrocetin was purified as described elsewhere.…”

Section: Cell Lines Antibodies and Reagentsmentioning

confidence: 99%

Functional analysis of the C-terminal flanking sequence of platelet glycoprotein Ibα using canine–human chimeras

Shen

Dong

Romo

et al. 2002

Blood

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Platelet glycoprotein Ib-IX-V (GPIb-IX-V) mediates adhesion to von Willebrand factor (vWF) in (patho)physiological thrombus formation. vWF binds the N-terminal 282 residues of GPIb␣, consisting of an N-terminal flank (His1-Ile35), 7 leucinerich repeats (Leu36-Ala200), a C-terminal flank (Phe201-Gly268), and a sulfated tyrosine sequence (Asp269-Glu282). By expressing canine-human chimeras of GPIb␣ on Chinese hamster ovary cells, binding sites for functional anti-GPIb␣ antibodies to individual domains were previously mapped, and it was shown that leucine-rich repeats 2 to 4 were required for optimal vWF recognition under static or flow conditions. Using novel canine-human chimeras dissecting the Cterminal flank, it is now demonstrated that (1) Phe201-Glu225 contains the epitope for AP1, an anti-GPIb␣ monoclonal antibody that inhibits both ristocetin-and botrocetindependent vWF binding; (2) VM16d, an antibody that preferentially inhibits botrocetindependent vWF binding, recognizes the sequence Val226-Gly268, surrounding Cys248, which forms a disulfide-bond with Cys209; (3) vWF binding to chimeric GPIb␣ is comparable to wild-type in 2 chimeras in which the sixth leucine-rich repeat was of the same species as the first disulfide loop (Phe201-Cys248) of the C-terminal flank, suggesting an interaction between these domains may be important for optimal vWF binding; and (4)

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Characterization of an antiglycoprotein Ib monoclonal antibody that specifically inhibits platelet-thrombin interaction

Cited by 49 publications

References 18 publications

Aggretin, a Heterodimeric C-type Lectin from Calloselasma rhodostoma (Malayan Pit Viper), Stimulates Platelets by Binding to α2β1 Integrin and Glycoprotein Ib, Activating Syk and Phospholipase Cγ2, but Does Not Involve the Glycoprotein VI/Fc Receptor γ Chain Collagen Receptor

Aggretin, a Heterodimeric C-type Lectin from Calloselasma rhodostoma (Malayan Pit Viper), Stimulates Platelets by Binding to α2β1 Integrin and Glycoprotein Ib, Activating Syk and Phospholipase Cγ2, but Does Not Involve the Glycoprotein VI/Fc Receptor γ Chain Collagen Receptor

Physical proximity and functional interplay of PECAM-1 with the Fc receptor FcγRIIa on the platelet plasma membrane

Functional analysis of the C-terminal flanking sequence of platelet glycoprotein Ibα using canine–human chimeras

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