Abstract:
:Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2β1, or to defects in downstream signalling events by comparison to platelet activation by C-type lectin-like receptor 2 (CLEC-2). GPVI and CLEC-2 activate a Src- and Syk-dependent signalling pathway upstream of phospholipase C (PLC) γ2. Phosphorylation of a conserved YxxL sequence known as a (hemi) immunotyrosine-based-activation-motif (ITAM) in both receptors is critical for Syk activation. Platelets from human pre-term and full-term neonates display mildly reduced expression of GPVI and CLEC-2, as well as integrin αIIbβ3, accounted for at the transcriptional level. They are also hypo-responsive to the two ITAM receptors, as shown by measurement of integrin αIIbβ3 activation, P-selectin expression and Syk and PLCγ2 phosphorylation. Mouse platelets are also hypo-responsive to GPVI and CLEC-2 from late gestation to 2 weeks of age, as determined by measurement of integrin αIIbβ3 activation. In contrast, the response to G protein-coupled receptor agonists was only mildly reduced and in some cases not altered in neonatal platelets of both species. A reduction in response to GPVI and CLEC-2, but not protease-activated receptor 4 (PAR-4) peptide, was also observed in adult mouse platelets following immune thrombocytopenia, whereas receptor expression was not impaired. Our results demonstrate developmental differences in platelet responsiveness to GPVI and CLEC-2, and also following immune platelet depletion leading to reduced Syk activation. The rapid generation of platelets during development or following platelet depletion is achieved at the expense of signalling by ITAM-coupled receptors.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Hardy AT,Palma-Barqueros V,Watson SK,Malcor JD,Eble JA,Gardiner EE,Blanco JE,Guijarro-Campillo R,Delgado JL,Lozano ML,Teruel-Montoya R,Vicente V,Watson SP,Rivera J,Ferrer-Marín Fdoi
10.1055/s-0038-1646924subject
Has Abstractpub_date
2018-06-01 00:00:00pages
1009-1020issue
6eissn
0340-6245issn
2567-689Xjournal_volume
118pub_type
杂志文章abstract::The terms glycoprotein IV (GPIV) and glycoprotein IIIb (GPIIIb) have been used interchangeably and reports in the literature have indicated this glycoprotein as having a molecular weight variously described as either 88,000 or 97,000, a fast anodal mobility on crossed electrophoresis and either 13 or less than 1 methi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-02-19 00:00:00
abstract::An amidrazonophenylalanine derivative, LB30057, inhibits the catalytic activity of thrombin potently by interaction with the active site of thrombin, and has high water solubility. In the present study, we evaluated the effect of LB30057 on the biological activities of thrombin at various tissues, and determined wheth...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2003-01-01 00:00:00
abstract::The surface of the platelet expresses procoagulant phospholipids that bind coagulation factors and contribute to the procoagulant activity of the cell. The evidence, however, also suggests that platelets may possess specific receptors for coagulation Factors V(a) and VIII(a). Examination of a limited set of the availa...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1993-07-01 00:00:00
abstract::Molsidomine and its active metabolite SIN-1 were examined in humans and animals for platelet suppressant and fibrinolytic activities. Following oral administration of molsidomine at doses of 6 or 15 mg/kg to rabbits, their blood platelets in PRP ex vivo required higher threshold concentrations of ADP, AA and thrombin ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-12-17 00:00:00
abstract::Although intravital microscopy models of thrombosis in mice have contributed to dissect the mechanisms of thrombus formation and stability, they have not been well adapted to study long-term evolution of occlusive thrombi. Here, we assessed the suitability of the dorsal skinfold chamber (DSC) for the study of thrombol...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH11-10-0705
更新日期:2012-05-01 00:00:00
abstract::There is much debate over the appropriateness of prescribing prolonged anticoagulation to heterozygous carriers of factor V Leiden suffering a first episode of deep vein thrombosis (DVT). We, thus used meta-analysis to estimate from six eligible studies the summary odds-ratio of recurrent DVT in carriers of factor V L...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::The etiology and pathophysiology of cerebral sinus venous thrombosis (CSVT) in the paediatric population is still poorly understood, and the role of thrombophilic risk factors remains to be elucidated. In our multi-center case-controlled study we studied 46 patients with CSVT diagnosed from April 1996 to December 2003...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH04-03-0182
更新日期:2004-10-01 00:00:00
abstract::The liver can be injured and its functions altered by activation of the coagulation and inflammatory processes in sepsis. The objective of the present study was to investigate the pattern of protease- activated receptors (PARs) over time in a model of acute liver injury induced by lipopolysaccharide (LPS); and whether...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2006-12-01 00:00:00
abstract::It has been reported that lanosterol can sensitize isolated rat platelets to agonists such as ADP and thrombin (4). The purpose of this paper was to determine whether lanosterol had similar effects on human platelets and whether this was achieved by changes in membrane fluidity. Lanosterol did increase the sensitivity...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-12-17 00:00:00
abstract::The demographic and clinical characteristics of adults and children with lower extremity deep-vein thrombosis and/or pulmonary embolism (LE DVT/PE) may differ from those with abdominal vein thrombosis (abdominal VT). Abdominal VT can be a presenting sign of an underlying prothrombotic state, and its presence in the se...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH12-08-0568
更新日期:2013-04-01 00:00:00
abstract::Antiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and beta2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. How...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::Venous thromboembolism (VTE) is a multifactorial disease. Major provoking factors (e. g. surgery, cancer, major trauma, and immobilisation) are identified in 50-60 % of patients, while the remaining cases are classified as unprovoked. However, minor predisposing conditions may be detectable in these patients, possibly...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-06-0563
更新日期:2015-06-01 00:00:00
abstract::Patients with atrial fibrillation at moderate to high risk of stroke are not always anticoagulated despite a lack of contraindications to vitamin K antagonists (VKAs) like warfarin. These patients are treated with aspirin, aspirin-clopidogrel combination therapy or even receive no thromboprophylaxis. The oral direct t...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析
doi:10.1160/TH10-10-0642
更新日期:2010-12-01 00:00:00
abstract::The redistribution of platelet glycoproteins (GP) Ib, IIb and IIIa in response to stimulation with human platelet specific alloantibodies, autoantibodies and a quinidine-dependent antibody was investigated using immunofluorescence and a quantitative radioimmunoassay. The platelet GPs carrying the corresponding epitope...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-10-28 00:00:00
abstract::Various tests were evaluated for their capacity to differentiate between platelet suspensions with different degrees of cell damage. Those suspensions were prepared by simultaneous isolation of platelets from the same platelet-rich plasma (PRP) using the following procedures: 1. centrifugation at 4 degrees C with EDTA...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-02-28 00:00:00
abstract:STUDY OBJECTIVE:Cytokines increase endothelial tissue factor (TF) and tissue plasminogen activator inhibitor type-1 (PAI-1) expression in vitro. Tissue factor interacts with factor VII to facilitate thrombosis and PAI-1 inhibits fibrinolysis by endogenous plasminogen activators. Because cytokine release is increased in...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract::The biologically active components from Viperidae venoms specifically affect cell-matrix interactions, and have been utilized for developing anti-adhesive therapy as anti-thrombotic and anti-angiogenic agents. Utilizing platelet aggregometry coupled with flow cytometry, we found that a metalloproteinase isolated from ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-07-0426
更新日期:2004-02-01 00:00:00
abstract::Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) were measured alongside flow-mediated vasodilation (FMD) in 34 patients with intermittent claudication and 14 control subjects. Patients with plasma sICAM-1 >253 ng/mL (median value) showed lower FMD than those with...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Severe postpartum haemorrhages (PPH) are responsible for maternal morbidity/mortality. Their complex management sometimes requires haemostatic supplementation, and therapeutic trials on fibrinogen or activated factor VII, which may add to the thrombotic risk, are currently being considered. Furthermore, there is a ris...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2008-11-01 00:00:00
abstract::Fibrinogen Matsumoto V (M-V) is a dysfibrinogen identified in a 52-year-old woman with systemic lupus erythematous. The triplet AGG encoding the amino acid residue Aalpha19 was replaced by GGG, resulting in the substitution of Arg-->Gly. Residue Aalpha19 has been shown to be one of the most important amino acids in th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Emicizumab, a bispecific monoclonal antibody, bridges activated factor IX (FIXa) and FX, replacing the function of missing FVIIIa to restore effective hemostasis in persons with hemophilia A (PwHA). Here we assess pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers in PwHA with FVIII inhibitors in the Phase III H...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1717114
更新日期:2020-10-21 00:00:00
abstract::Antithrombin (AT) is a protein of the serpin superfamily involved in regulation of the proteolytic activity of the serine proteases of the coagulation system. AT is known to exhibit anti-inflammatory and cardioprotective properties when it binds to heparan sulfate proteoglycans (HSPGs) on vascular cells. AMP-activated...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-04-0360
更新日期:2015-02-01 00:00:00
abstract::Hemin is a heme oxygenase-1 (HO-1) inducer which provides endogenous carbon monoxide known for playing roles in cell proliferation, inflammation or aggregation process. The objective of the current study was to examine the effect of prophylactic treatment with hemin in a thrombosis vascular model. Three groups of Wist...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Recombinant hirudin, a pure, specific antithrombin could be more effective than heparin in the treatment of deep vein thrombosis, but its short half-life requires constant intravenous infusion, whereas subcutaneous administration of recombinant hirudin can ensure stable and prolonged plasma levels. The aim o...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::The major plasmin inhibitors namely alpha2-plasmin inhibitor and alpha2-macroglobulin were compared for their effects on lysis of fibrin clot. Plasmin fibrinolytic activity was immediately inhibited by alpha2-plasmin inhibitor, whereas alpha2-macroglobulin inhibited plasmin progressively. Urokinase(plasminogen activat...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-02-28 00:00:00
abstract::We have established a new, enzyme-linked immunosorbent assay (ELISA) for the detection of ADAMTS13 antigen using purified polyclonal rabbit anti-human ADAMTS13 IgG. Normal plasma ADAMTS13 antigen levels span a concentration of 740-1420 ng/ml (median 1080 ng/ml) resulting in an ADAMTS13 activity to antigen ratio of 0.4...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-08-0550
更新日期:2006-02-01 00:00:00
abstract::Despite reports that Tris [tris (hydroxymethyl)aminomethane] affects platelets, it is often used to buffer suspending media. Human or rabbit platelets were washed and resuspended in Tyrode solution containing apyrase and 0.35% albumin. Addition of 15 mM Tris partially inhibited primary aggregation induced by 10 microM...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-04-30 00:00:00
abstract::Vascular endothelial cells perform many differentiated functions in processes such as angiogenesis, hemostasis, and inflammation. The number of recognized differentiated functions has increased rapidly in recent years, but there may be many more still unrecognized. The purpose of this study is to estimate the fraction...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-05-03 00:00:00
abstract:OBJECTIVE:To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa; NovoSeven) in the home setting for mild to moderately severe joint, muscle; and mucocutaneous bleeding episodes in patients with haemophilia A or B with inhibitors. DESIGN:Multicentre, open-label, single arm, phase...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1998-12-01 00:00:00
abstract::ADP or thrombin caused a transient change in creatine phosphate (CP) content of rat platelets. At 25 degrees C the CP content decreased most 30 sec after the addition of ADP or thrombin and recovered thereafter. ATP or AMP was without effect. The rat platelets aggregated at 25 degrees C by ADP or thrombin, but the cha...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-08-31 00:00:00