Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations by Bénédicte Dumont, Dominique Lasne, Chantal Rothschild,

Slides:

Advertisements

Similar presentations

Human platelets produced in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice upon transplantation of human cord blood CD34+ cells are.

Advertisements

Activation of factor XI by products of prothrombin activation

by Matilde Murga, Oscar Fernandez-Capetillo, and Giovanna Tosato

Reduced thrombus stability in mice lacking the α2A-adrenergic receptor

Activation of αIIbβ3 is a sufficient but also an imperative prerequisite for activation of α2β1 on platelets by Gerlinde R. Van de Walle, Anne Schoolmeester,

by Matt W. Goschnick, Lai-Man Lau, Janet L. Wee, Yong S. Liu, P

Arg2074Cys missense mutation in the C2 domain of factor V causing moderately severe factor V deficiency: molecular characterization by expression of the.

Tissue-Specific Expression of Functional Platelet Factor XI Is Independent of Plasma Factor XI Expression by Chang-jun Hu, Frank A. Baglia, David C.B.

Transglutaminase-mediated oligomerization of the fibrin(ogen) αC domains promotes integrin-dependent cell adhesion and signaling by Alexey M. Belkin, Galina.

Defective release of α granule and lysosome contents from platelets in mouse Hermansky-Pudlak syndrome models by Ronghua Meng, Jie Wu, Dawn C. Harper,

Vessel wall BAMBI contributes to hemostasis and thrombus stability

Shielding the front-strand β3 of the von Willebrand factor A1 domain inhibits its binding to platelet glycoprotein Ibα by Arnaud Bonnefoy, Hiroshi Yamamoto,

by Kesheng Dai, Richard Bodnar, Michael C. Berndt, and Xiaoping Du

by Hong Yin, Aleksandra Stojanovic, Nissim Hay, and Xiaoping Du

by Mineo Iwata, Lynn Graf, Norihiro Awaya, and Beverly Torok-Storb

Missense Mutations of the Glycoprotein (GP) Ibβ Gene Impairing the GPIb α/β Disulfide Linkage in a Family With Giant Platelet Disorder by Shinji Kunishima,

Recombinant factor VIIa restores aggregation of αIIbβ3-deficient platelets via tissue factor–independent fibrin generation by Ton Lisman, Jelle Adelmeijer,

Effects of inflammatory cytokines on the release and cleavage of the endothelial cell–derived ultralarge von Willebrand factor multimers under flow by.

Molecular characterization of in-frame and out-of-frame alternative splicings in coagulation factor XI pre-mRNA by Rosanna Asselta, Valeria Rimoldi, Ilaria.

Janina Jamasbi et al. BTS 2016;1:

ADAP interactions with talin and kindlin promote platelet integrin αIIbβ3 activation and stable fibrinogen binding by Ana Kasirer-Friede, Jian Kang, Bryan.

Agonist-induced aggregation of Chinese hamster ovary cells coexpressing the human receptors for fibrinogen (integrin αIIbβ3) and the platelet-activating.

by Veerendra Munugalavadla, Jovencio Borneo, David A

by Jun Chung, Xue-Qing Wang, Frederik P. Lindberg, and William A

Analysis of the storage and secretion of von Willebrand factor in blood outgrowth endothelial cells derived from patients with von Willebrand disease by.

by Laurent O. Mosnier, Paula Buijtenhuijs, Pauline F. Marx, Joost C. M

A role for the thiol isomerase protein ERP5 in platelet function

T-cell activation and cytokine production via a bispecific single-chain antibody fragment targeted to blood-stage malaria parasites by Shigeto Yoshida,

Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity by Ju Hyun Cho, Iain P. Fraser, Koichi Fukase, Shoichi.

Integrin-linked kinase associated with integrin activation

Rap1-GTP–interacting adaptor molecule (RIAM) is dispensable for platelet integrin activation and function in mice by Simon Stritt, Karen Wolf, Viola Lorenz,

by Bruno Bernardi, Gianni F. Guidetti, Francesca Campus, Jill R

The γ-carboxyglutamic acid domain of anticoagulant protein S is involved in activated protein C cofactor activity, independently of phospholipid binding.

Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection by Richard J. Pleass, Solabomi A. Ogun, David.

Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2)‏ by Achille Iolascon, Maria d'Apolito, Veronica.

Β1 integrin−mediated signals are required for platelet granule secretion and hemostasis in mouse by Tobias Petzold, Raphael Ruppert, Dharmendra Pandey,

Impaired activation of platelets lacking protein kinase C-θ isoform

A Point Mutation Thr799Met on the 2 Integrin Leads to the Formation of New Human Platelet Alloantigen Sita and Affects Collagen-Induced Aggregation by.

Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro by José Perdomo, Feng Yan,

Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia by Lubica Rauova, Mortimer Poncz, Steven E.

C1qTNF–related protein-1 (CTRP-1): a vascular wall protein that inhibits collagen-induced platelet aggregation by blocking VWF binding to collagen by Gerald.

by Guang Yang, Shu-Ching Huang, Jane Y. Wu, and Edward J. Benz

A Three Amino Acid Deletion in Glycoprotein IIIa Is Responsible for Type I Glanzmann's Thrombasthenia: Importance of Residues Ile325Pro326Gly327 for β3.

Ristocetin-dependent, but not botrocetin-dependent, binding of von Willebrand factor to the platelet glycoprotein Ib-IX-V complex correlates with shear-dependent.

Conservative mutations in the C2 domains of factor VIII and factor V alter phospholipid binding and cofactor activity by Gary E. Gilbert, Valerie A. Novakovic,

Interaction of kindlin-3 and β2-integrins differentially regulates neutrophil recruitment and NET release in mice by Zhen Xu, Jiayi Cai, Juan Gao, Gilbert.

Structural and Functional Characterization of Factor H Mutations Associated with Atypical Hemolytic Uremic Syndrome Pilar Sánchez-Corral, David Pérez-Caballero,

Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor by Anne F. Riddell,

Regulation of plasminogen activation: a role for melanotransferrin (p97) in cell migration by Michel Demeule, Yanick Bertrand, Jonathan Michaud-Levesque,

Volume 135, Issue 2, Pages e1 (August 2008)

In-depth PtdIns(3,4,5)P3 signalosome analysis identifies DAPP1 as a negative regulator of GPVI-driven platelet function by Tom N. Durrant, James L. Hutchinson,

Dichloroacetate, an inhibitor of pyruvate dehydrogenase kinases, inhibits platelet aggregation and arterial thrombosis by Manasa K. Nayak, Nirav Dhanesha,

Pnut is phosphorylated during early Drosophila embryogenesis.

Janina Jamasbi et al. BTS 2016;1:

A function-blocking PAR4 antibody is markedly antithrombotic in the face of a hyperreactive PAR4 variant by Shauna L. French, Claudia Thalmann, Paul F.

Volume 97, Issue 2, Pages (July 2009)

The 130-kDa Glycoform of CD43 Functions as an E-Selectin Ligand for Activated Th1 Cells In Vitro and in Delayed-Type Hypersensitivity Reactions In Vivo

Multiple distinct molecular mechanisms influence sensitivity and resistance to MDM2 inhibitors in adult acute myelogenous leukemia by Jianting Long, Brian.

by Changjie Zhang, Anju Kelkar, and Sriram Neelamegham

Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib by Alexander P. Bye, Amanda J. Unsworth,

Janina Jamasbi et al. BTS 2016;1:

T exosomes bind MAdCAM-1 via RA-increased integrin α4β7.

Defective RAB1B-related megakaryocytic ER-to-Golgi transport in RUNX1 haplodeficiency: impact on von Willebrand factor by Gauthami Jalagadugula, Lawrence.

The Inhibitory Receptor LIR-1 Uses a Common Binding Interaction to Recognize Class I MHC Molecules and the Viral Homolog UL18 Tara L Chapman, Astrid.

Synthetic glycopolymers require GPIbα to induce full aggregation in murine and human platelets. Synthetic glycopolymers require GPIbα to induce full aggregation.

by Alyssa J. Moroi, Nicole M. Zwifelhofer, Matthew J. Riese, Debra K

Fibrinogen fragments and platelet dysfunction in uremia

Lamellarin D induces cell death through a Fas-independent pathway.

Interleukin-17 is Produced by Both Th1 and Th2 Lymphocytes, and Modulates Interferon-γ- and Interleukin-4-Induced Activation of Human Keratinocytes Cristina.

Design of lipid-binding deficient mutants of α-synuclein.

Presentation transcript:

Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations by Bénédicte Dumont, Dominique Lasne, Chantal Rothschild, Maxime Bouabdelli, Véronique Ollivier, Claire Oudin, Nadine Ajzenberg, Bernard Grandchamp, and Martine Jandrot-Perrus Blood Volume 114(9):1900-1903 August 27, 2009 ©2009 by American Society of Hematology

Platelet functional analysis. Platelet functional analysis. (A) Platelet aggregation was measured by turbidimetry on PRP from a control subject and the patient. PRP was stimulated by 5 μM adenosine diphosphate (green) and 1 μg/mL collagen (red). (B) Thrombus formation on collagen under blood flow was analyzed using DiOC6-labeled platelets in whole blood perfused at a shear rate of 500 second−1 over a collagen-coated coverslip during 5 minutes. Thrombus formation was visualized in real-time using an inverted microscope (Leica DMIRB) using a lens at 100× and a 488 nm filter. Images were acquired using a DP30BW camera and CellP software (Olympus) and processed with Histolab software (Microvision). Areas covered by platelet thrombi were measured on 10 different, randomly chosen, microscopic fields. (C) Thrombin generation was triggered by the addition of tissue factor (1 pM) to PRP after incubation with 5 μg/mL collagen. Results are from 1 experiment performed in triplicate, representative of 2 independent experiments. Bénédicte Dumont et al. Blood 2009;114:1900-1903 ©2009 by American Society of Hematology

Characterization of the patient's GPVI molecular defect. Characterization of the patient's GPVI molecular defect. (A) Flow cytometry on whole blood using the monoclonal antibody 3J24.2 showed decreased GPVI expression on the patient's platelets, compared with control. (B) Serial quantities of proteins in sodium dodecyl sulfate–platelet lysate from the patient or a control were immunoblotted with a human polyclonal anti-GPVI (hpAb). GPVI of the control migrated as a single 58-kDa band, whereas the patient's GPVI migrated as a smear and presented a partial deficiency (note that the 10-μg control GPVI band is saturated; the 35-kDa band is nonspecific). When 10 μg control and patient platelet proteins were immunoblotted with monoclonal antibody 3J24.2 or 9O12.2, the patient's GPVI was hardly detectable. (C) DNA sequence showing the single nucleotide substitution in exon 3 (C172T), resulting in the Arg38 substitution in Cys. (D) Purified recombinant wild-type (WT) and R38C GPVI-Fc were analyzed on sodium dodecyl sulfate–8% acrylamide gels and Coomassie blue staining. WT GPVI-Fc migrated as an approximately 220-kDa band and R38C GPVI-Fc as a smear in nonreducing conditions (NR), and both migrated as a major 95-kDa band after reduction with 5% β-mercaptoethanol (R). (E) Binding of WT and R38C GPVI-Fc to immobilized collagen. Results represent mean ± SD of 2 experiments performed in triplicate. The Kd values are 1.67 ± 0.26 μg/mL and 1.4 ± 0.17 μg/mL for R38C and WT GPVI-Fc, respectively. (F) Three-dimensional structure of the extracellular domain of GPVI with localization of R38. R38 and other important residues for collagen binding, such as K59, K41, and R166,6 are localized on the extracellular domain of GPVI as crystallized by Horii et al.8 The 2 disulfide bridges are represented and encircled in black. Bénédicte Dumont et al. Blood 2009;114:1900-1903 ©2009 by American Society of Hematology