von Willebrand factor (VWF) propeptide binding to VWF D'D3 domain attenuates platelet activation and adhesion.

Abstract:

:Noncovalent association between the von Willebrand factor (VWF) propeptide (VWFpp) and mature VWF aids N-terminal multimerization and protein compartmentalization in storage granules. This association is currently thought to dissipate after secretion into blood. In the present study, we examined this proposition by quantifying the affinity and kinetics of VWFpp binding to mature VWF using surface plasmon resonance and by developing novel anti-VWF D'D3 mAbs. Our results show that the only binding site for VWFpp in mature VWF is in its D'D3 domain. At pH 6.2 and 10mM Ca(2+), conditions mimicking intracellular compartments, VWFpp-VWF binding occurs with high affinity (K(D) = 0.2nM, k(off) = 8 × 10(-5) s(-1)). Significant, albeit weaker, binding (K(D) = 25nM, k(off) = 4 × 10(-3) s(-1)) occurs under physiologic conditions of pH 7.4 and 2.5mM Ca(2+). This interaction was also observed in human plasma (K(D) = 50nM). The addition of recombinant VWFpp in both flow-chamber-based platelet adhesion assays and viscometer-based shear-induced platelet aggregation and activation studies reduced platelet adhesion and activation partially. Anti-D'D3 mAb DD3.1, which blocks VWFpp binding to VWF-D'D3, also abrogated platelet adhesion, as shown by shear-induced platelet aggregation and activation studies. Our data demonstrate that VWFpp binding to mature VWF occurs in the circulation, which can regulate the hemostatic potential of VWF by reducing VWF binding to platelet GpIbα.

journal_name

Blood

journal_title

Blood

authors

Madabhushi SR,Shang C,Dayananda KM,Rittenhouse-Olson K,Murphy M,Ryan TE,Montgomery RR,Neelamegham S

doi

10.1182/blood-2011-10-387548

subject

Has Abstract

pub_date

2012-05-17 00:00:00

pages

4769-78

issue

20

eissn

0006-4971

issn

1528-0020

pii

blood-2011-10-387548

journal_volume

119

pub_type

杂志文章

相关文献

BLOOD文献大全
  • p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11;14)(q13;q32).

    abstract::The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular marker that serves as an indicator of tumor progression or clinical prognosis has ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Louie DC,Offit K,Jaslow R,Parsa NZ,Murty VV,Schluger A,Chaganti RS

    更新日期:1995-10-15 00:00:00

  • Effect of interleukin-1 beta converting enzyme inhibitor on acute myelogenous leukemia progenitor proliferation.

    abstract::Interleukin-1 beta (IL-1 beta) converting enzyme (ICE) is a cysteine protease that specifically cleaves precursor IL-1 beta to its biologically active form. Recent studies have also implicated ICE in the induction of apoptosis in vertebrate cells. Because IL-1 plays a major role in acute myelogenous leukemia (AML) bla...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Estrov Z,Black RA,Sleath PR,Harris D,Van Q,LaPushin R,Estey EH,Talpaz M

    更新日期:1995-12-15 00:00:00

  • Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits.

    abstract::Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Agnelli G,Buchanan MR,Fernandez F,Van Ryn J,Hirsh J

    更新日期:1985-08-01 00:00:00

  • HIV-1 reprograms the migration of macrophages.

    abstract::Macrophages are motile leukocytes, targeted by HIV-1, thought to play a critical role in host dissemination of the virus. However, whether infection impacts their migration capacity remains unknown. We show that 2-dimensional migration and the 3-dimensional (3D) amoeboid migration mode of HIV-1-infected human monocyte...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-08-596775

    authors: Vérollet C,Souriant S,Bonnaud E,Jolicoeur P,Raynaud-Messina B,Kinnaer C,Fourquaux I,Imle A,Benichou S,Fackler OT,Poincloux R,Maridonneau-Parini I

    更新日期:2015-03-05 00:00:00

  • Oligodeoxynucleotide-mediated inhibition of c-myb gene expression in autografted bone marrow: a pilot study.

    abstract::Antisense oligodeoxynucleotide (ODN) drugs might be more effective if their delivery was optimized and they were targeted to short-lived proteins encoded by messenger RNA (mRNA) species with equally short half-lives. To test this hypothesis, an ODN targeted to the c-myb proto-oncogene was developed and used to purge m...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood.v99.4.1150

    authors: Luger SM,O'Brien SG,Ratajczak J,Ratajczak MZ,Mick R,Stadtmauer EA,Nowell PC,Goldman JM,Gewirtz AM

    更新日期:2002-02-15 00:00:00

  • Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B-severe combined immune deficiency or Omenn syndrome.

    abstract::Omenn syndrome (OS) is an inherited disorder characterized by an absence of circulating B cells and an infiltration of the skin and the intestine by activated oligoclonal T lymphocytes, indicating that a profound defect in the lymphoid developmental program could be accountable for this condition. Inherited mutations ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.9.2772

    authors: Corneo B,Moshous D,Güngör T,Wulffraat N,Philippet P,Le Deist FL,Fischer A,de Villartay JP

    更新日期:2001-05-01 00:00:00

  • A recombinant murine meizothrombin precursor, prothrombin R157A/R268A, inhibits thrombosis in a model of acute carotid artery injury.

    abstract::Mutations in human prothrombin that generate a stable form of meizothrombin or meizothrombin(desF1) cause dysprothrombinemia in both the homozygous and heterozygous state, suggesting that meizothrombin has dominant anticoagulant effects in vivo. The enzymatic characterization of recombinant mouse meizothrombin, meizot...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-02-0478

    authors: Shim K,Zhu H,Westfield LA,Sadler JE

    更新日期:2004-07-15 00:00:00

  • CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date.

    abstract::Adoptive transfer of T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 has produced impressive results in treating patients with B-cell malignancies. Although these CAR-modified T cells target the same antigen, the designs of CARs vary as well as several key aspects of the clinic...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2016-02-629063

    authors: Park JH,Geyer MB,Brentjens RJ

    更新日期:2016-06-30 00:00:00

  • High serum levels of soluble interleukin 2 receptor in patients with B chronic lymphocytic leukemia.

    abstract::By using an enzyme-linked immunosorbent assay, the presence of the soluble form of the interleukin-2 receptor (sIL-2R) was evaluated in the peripheral blood of 54 patients with B cell chronic lymphocytic leukemia (B-CLL). Serum levels of sIL-2R were correlated with clinical features, relevant hematologic and immunolog...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Semenzato G,Foa R,Agostini C,Zambello R,Trentin L,Vinante F,Benedetti F,Chilosi M,Pizzolo G

    更新日期:1987-08-01 00:00:00

  • Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo.

    abstract::Toll-like receptors (TLRs) are able to interact with pathogen-derived products and their signals induce the coordinated activation of innate and adaptive immune mechanisms. Dendritic cells (DCs) play a central role in these events. As the different TLRs are able to trigger MyD88/TRIF-dependent and -independent signali...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-10-4015

    authors: Warger T,Osterloh P,Rechtsteiner G,Fassbender M,Heib V,Schmid B,Schmitt E,Schild H,Radsak MP

    更新日期:2006-07-15 00:00:00

  • Analysis of fibrinogen gamma-chain truncations shows the C-terminus, particularly gammaIle387, is essential for assembly and secretion of this multichain protein.

    abstract::To examine the role of the fibrinogen gamma chain in the assembly and secretion of this multichain protein, we synthesized a series of fibrinogen variants with truncated gamma chains, terminating between residues gamma379 and the C-terminus, gamma411. The variant fibrinogens were synthesized from altered gamma-chain c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.10.3654

    authors: Okumura N,Terasawa F,Tanaka H,Hirota M,Ota H,Kitano K,Kiyosawa K,Lord ST

    更新日期:2002-05-15 00:00:00

  • Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations.

    abstract::BMS-354825 (dasatinib) and AMN107 (nilotinib) are potent alternate Abl inhibitors with activity against many imatinib mesylate-resistant BCR-ABL kinase domain (KD) mutants, except T315I. We used N-ethyl-N-nitrosourea (ENU)-exposed Ba/F3-p210(BCR-ABL) cells to compare incidence and types of KD mutants emerging in the p...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-02-004580

    authors: Bradeen HA,Eide CA,O'Hare T,Johnson KJ,Willis SG,Lee FY,Druker BJ,Deininger MW

    更新日期:2006-10-01 00:00:00

  • Liver X receptors regulate dendritic cell phenotype and function through blocked induction of the actin-bundling protein fascin.

    abstract::Liver X receptors (LXRs) are nuclear receptors regulating lipid and cholesterol metabolism. Recent data revealed a cross talk between LXR and Toll-like receptor signaling in macrophages, indicating a role in immunity. Here, we show that LXRalpha is expressed in human myeloid dendritic cells (DCs) and induced during di...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-08-043422

    authors: Geyeregger R,Zeyda M,Bauer W,Kriehuber E,Säemann MD,Zlabinger GJ,Maurer D,Stulnig TM

    更新日期:2007-05-15 00:00:00

  • Monoclonal antibody definition of T cell acute leukemia: a Pediatric Oncology Group study.

    abstract::Leukemic blasts from 774 children with newly diagnosed acute lymphocytic leukemia (ALL) have been phenotyped by microcytotoxicity testing with a panel of monoclonal antibodies and heteroantisera as part of a Pediatric Oncology Group classification study of acute leukemia. One hundred twenty-two cases, or 16% were desi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Borowitz MJ,Dowell BL,Boyett JM,Falletta JM,Pullen DJ,Crist WM,Humphrey GB,Metzgar RS

    更新日期:1985-04-01 00:00:00

  • Recombinant toxins containing human granulocyte-macrophage colony-stimulating factor and either pseudomonas exotoxin or diphtheria toxin kill gastrointestinal cancer and leukemia cells.

    abstract::The granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is a potential target for toxin-directed therapy, because it is overexpressed on many leukemias and solid tumors and apparently not on stem cells. To investigate the potential therapeutic use of GM-CSF toxins, we fused human GM-CSF to truncated fo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kreitman RJ,Pastan I

    更新日期:1997-07-01 00:00:00

  • The human Kell blood group gene maps to chromosome 7q33 and its expression is restricted to erythroid cells.

    abstract::The Kell blood group is one of the major antigenic systems in human red blood cells. To determine the location of the Kell gene on human chromosomes, panels containing genomic DNA of human-hamster somatic cell hybrids were hybridized with radiolabeled cDNA probe specific for the Kell locus. Only the samples containing...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lee S,Zambas ED,Marsh WL,Redman CM

    更新日期:1993-05-15 00:00:00

  • Long-term outcomes after autologous stem cell transplantation for patients with POEMS syndrome (osteosclerotic myeloma): a single-center experience.

    abstract::The POEMS syndrome (polyradiculoneuropathy, organomegaly, multiple endocrinopathies, monoclonal protein, skin changes) is a rare disease associated with a plasma cell dyscrasia. Patients with disseminated POEMS can be treated with high-dose therapy and autologous stem cell transplantation (ASCT). While clinical improv...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-04-423178

    authors: D'Souza A,Lacy M,Gertz M,Kumar S,Buadi F,Hayman S,Dingli D,Zeldenrust S,Kyle R,Ansell S,Inwards D,Johnston P,Micallef I,Porrata L,Litzow M,Gastineau D,Hogan W,Dispenzieri A

    更新日期:2012-07-05 00:00:00

  • The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells.

    abstract::The association of fibroblast growth factor receptor 3 (FGFR3) expression with t(4;14) multiple myeloma (MM) and the demonstration of the transforming potential of this receptor tyrosine kinase (RTK) make it a particularly attractive target for drug development. We report here a novel and highly specific anti-FGFR3-ne...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-10-4179

    authors: Trudel S,Stewart AK,Rom E,Wei E,Li ZH,Kotzer S,Chumakov I,Singer Y,Chang H,Liang SB,Yayon A

    更新日期:2006-05-15 00:00:00

  • Synergism between recombinant growth factors, GM-CSF and G-CSF, acting on the blast cells of acute myeloblastic leukemia.

    abstract::The genes for the hemopoietic growth factors, GM colony-stimulating factor (CSF) and G-CSF have been cloned, and recombinant material is available for both. We tested these recombinant factors for their effects on the blast cells of acute myeloblastic leukemia (AML). Culture methods are available that support both col...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kelleher C,Miyauchi J,Wong G,Clark S,Minden MD,McCulloch EA

    更新日期:1987-05-01 00:00:00

  • Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells.

    abstract::Serotonin (5-hydroxytryptamine, or 5-HT), released from activated platelets, not only accelerates aggregation of platelets but also is known to promote mitosis, migration, and contraction of vascular smooth muscle cells (VSMCs). These effects are considered to contribute to thrombus formation and atherosclerosis. The ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.6.1697

    authors: Kawano H,Tsuji H,Nishimura H,Kimura S,Yano S,Ukimura N,Kunieda Y,Yoshizumi M,Sugano T,Nakagawa K,Masuda H,Sawada S,Nakagawa M

    更新日期:2001-03-15 00:00:00

  • Fanconi anemia group J mutation abolishes its DNA repair function by uncoupling DNA translocation from helicase activity or disruption of protein-DNA complexes.

    abstract::Fanconi anemia (FA) is a genetic disease characterized by congenital abnormalities, bone marrow failure, and susceptibility to leukemia and other cancers. FANCJ, one of 13 genes linked to FA, encodes a DNA helicase proposed to operate in homologous recombination repair and replicational stress response. The pathogenic...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-11-256016

    authors: Wu Y,Sommers JA,Suhasini AN,Leonard T,Deakyne JS,Mazin AV,Shin-Ya K,Kitao H,Brosh RM Jr

    更新日期:2010-11-11 00:00:00

  • Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency.

    abstract::Omenn syndrome (OS) is a severe immunodeficiency associated with erythroderma, lymphoproliferation, elevated IgE, and hyperactive oligoclonal T cells. A restricted T-cell repertoire caused by defective thymic T-cell development and selection, lymphopenia with homeostatic proliferation, and lack of regulatory T cells a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-03-631374

    authors: Fuchs S,Rensing-Ehl A,Pannicke U,Lorenz MR,Fisch P,Jeelall Y,Rohr J,Speckmann C,Vraetz T,Farmand S,Schmitt-Graeff A,Krüger M,Strahm B,Henneke P,Enders A,Horikawa K,Goodnow C,Schwarz K,Ehl S

    更新日期:2015-10-01 00:00:00

  • VavP-Bcl2 transgenic mice develop follicular lymphoma preceded by germinal center hyperplasia.

    abstract::In human follicular lymphoma the t(14; 18) chromosome translocation activates the antiapoptotic oncogene Bcl2 by linking it to the immunoglobulin heavy chain (IGH) locus. Transgenic mice expressing Bcl2 controlled by an Igh enhancer (E mu) do not develop follicular lymphoma, although they do have an increased incidenc...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-07-2469

    authors: Egle A,Harris AW,Bath ML,O'Reilly L,Cory S

    更新日期:2004-03-15 00:00:00

  • Analysis of TNF-receptor and ligand superfamily molecules in patients with lymphoproliferative disease of granular lymphocytes.

    abstract::In 21 patients with lymphoproliferative disease of granular lymphocytes (LDGL), we investigated the expression and the function of molecules belonging to TNF-receptor and TNF-ligand superfamilies (CD30/CD30L; CD40/CD40L; CD27/CD70; Fas [CD95]/FasL[CD95L]). Fourteen patients were characterized by a proliferation of gra...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Zambello R,Trentin L,Facco M,Siviero M,Galvan S,Piazza F,Perin A,Agostini C,Semenzato G

    更新日期:2000-07-15 00:00:00

  • Characterization of influenza A virus activation of the human neutrophil.

    abstract::Neutrophil dysfunction consequent to influenza A virus infection has been described in vivo and in vitro and may contribute to the serious bacterial sequelae which occur in influenza-infected hosts. On the premise that such dysfunction may represent a form of "deactivation," we sought to characterize neutrophil activa...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hartshorn KL,Collamer M,White MR,Schwartz JH,Tauber AI

    更新日期:1990-01-01 00:00:00

  • Persistent epstein-barr virus infection mimicking juvenile chronic myelogenous leukemia: immunologic and hematologic studies.

    abstract::Epstein-Barr virus (EBV) infections may induce a diverse clinical picture, ranging from the well characterized infectious mononucleosis (IM) syndrome to the rare X-linked lymphoproliferative syndrome. We describe two unrelated children, a 21-mo-old white boy and a 15-mo-old black girl, who presented with the clinical ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Herrod HG,Dow LW,Sullivan JL

    更新日期:1983-06-01 00:00:00

  • Identification of the dombrock blood group glycoprotein as a polymorphic member of the ADP-ribosyltransferase gene family.

    abstract::Identification of the 25 known human blood group molecules is of fundamental importance for the fields of erythroid cell biology and transfusion medicine. Here we provide the first molecular description of the "Dombrock" blood group system. A candidate gene was identified by in silico analyses of approximately 5000 ex...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gubin AN,Njoroge JM,Wojda U,Pack SD,Rios M,Reid ME,Miller JL

    更新日期:2000-10-01 00:00:00

  • Pro-B-cell to pre-B-cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein.

    abstract::The most common chromosomal abnormality of infant acute lymphoblastic leukemia (ALL) is the t(4;11)(q21;q23) that gives rise to the MLL/AF4 fusion gene. Leukemic blasts expressing MLL/AF4 are arrested at an early progenitor stage with lymphoid or monocytoid characteristics. A novel B-lineage ALL cell line termed B-lin...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.12.3398

    authors: Bertrand FE,Vogtenhuber C,Shah N,LeBien TW

    更新日期:2001-12-01 00:00:00

  • Inhibition of ristocetin-induced platelet agglutination by vancomycin.

    abstract::Ristocetin and vancomycin are structurally similar glycopeptide antibiotics. Both vancomycin and ristocetin in high concentrations (3.0 mg/ml) cause the precipitation of fibrinogen, plasminogen, and IgG from platelet-poor plasma (PPP). In contrast to ristocetin, vanomycin (0.5-1.5 mg/ml) does not agglutinate platelets...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Moake JL,Cimo PL,Peterson DM,Roper P,Natelson EA

    更新日期:1977-09-01 00:00:00

  • Antitumor activity of CAR-T cells targeting the intracellular oncoprotein WT1 can be enhanced by vaccination.

    abstract::The recent success of chimeric antigen receptor (CAR)-T cell therapy for treatment of hematologic malignancies supports further development of treatments for both liquid and solid tumors. However, expansion of CAR-T cell therapy is limited by the availability of surface antigens specific for the tumor while sparing no...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2017-08-802926

    authors: Akahori Y,Wang L,Yoneyama M,Seo N,Okumura S,Miyahara Y,Amaishi Y,Okamoto S,Mineno J,Ikeda H,Maki T,Fujiwara H,Akatsuka Y,Kato T,Shiku H

    更新日期:2018-09-13 00:00:00