Abstract：
:Our initial finding that CD40- and CD40 ligand (CD40L)-deficient mice displayed prolonged tail bleeding and platelet function analyzer (PFA-100) closure times prompted us to further investigate the role of the CD40-CD40L dyad in primary hemostasis and platelet function. Recombinant human soluble CD40L (rhsCD40L), chemical cross-linking of which suggested a trimeric structure of the protein in solution, activated platelets in a CD40-dependent manner as evidenced by increased CD62P expression. CD40 monoclonal antibody (mAb) M3, which completely blocked rhsCD40L-induced platelet activation, also prolonged PFA-100 closure times of normal human blood. In contrast, CD40 mAb G28-5 showed less potential in blocking rhsCD40L-induced CD62P expression and did not affect PFA-100 closure times. However, when added to the platelets after rhsCD40L, G28-5 significantly enhanced the platelet response by causing clustering of, and signaling through, FcgammaRII. Similarly, higher order multimeric immune complexes formed at a 1/3 molar ratio of M90, a CD40L mAb, to rhsCD40L induced strong Fcgamma RII-mediated platelet activation when translocated to the platelet surface in a CD40-dependent manner, including the induction of morphological shape changes, fibrinogen binding, platelet aggregation, dense granule release, microparticle generation and monocyte-platelet-conjugate formation. The results suggest that CD40 may play a role in primary hemostasis and platelet biology by two independent mechanisms: First, by functioning as a primary signaling receptor for CD40L and, second, by serving as a docking molecule for CD40L immune complexes. The latter would also provide a potential mechanistic explanation for the unexpected high incidence of CD40L mAb-associated thrombotic events in recent human and animal studies.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Langer F,Ingersoll SB,Amirkhosravi A,Meyer T,Siddiqui FA,Ahmad S,Walker JM,Amaya M,Desai H,Francis JLdoi
10.1160/TH04-12-0774keywords:
subject
Has Abstractpub_date
2005-06-01 00:00:00pages
1137-46issue
6eissn
0340-6245issn
2567-689Xpii
05061137journal_volume
93pub_type
杂志文章abstract：:The novel fast inhibitor to tissue plasminogen activator in plasma has been determined in 20 healthy non-pregnant women, 48 apparently healthy pregnant women and 136 women with risk pregnancies (preeclampsia, suspected fetal growth retardation, thrombosis or previous history of thrombosis, diabetes and others). In hea...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-10-31 00:00:00
abstract：:The platelet integrin alpha(IIb)beta(3) mediates the final step of platelet aggregation that requires pre-activation through an inside-out signal initiated by agonists. Experiments conducted under static conditions using platelet-rich plasma show that platelet activation and adhesion activity of alpha(IIb)beta(3) are ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2008-11-01 00:00:00
abstract：:The cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgII is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a reco...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-01-23 00:00:00
abstract：:A procedure for using citrated fresh plasmas for International Sensitivity Index (ISI) calibration of two types of whole blood point-of-care test (POCT) prothrombin time (PT) monitor systems has been assessed in a multicentre study. The CoaguChek Mini and TAS PT-NC systems gave higher ISI with whole blood samples than...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：
更新日期：2002-05-01 00:00:00
abstract：:Inherited thrombophilic states are associated with an increased risk for deep vein thrombosis (DVT), but whether they are also risk factors for superficial vein thrombosis (SVT) is uncertain. We assessed the risk conferred by inherited thrombophilic states in patients with a first episode of SVT in whom the coexistenc...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:The behavior of direct fibrinolytic (non-plasmin) proteinase activity and plasminogen-activator activity in the lung and spleen was investigated in rats after a single intravenous injection of bacterial endotoxin, and the influence of thrombin inhibitors on the effects of the endotoxin was assessed. The non-plasmin fi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-06-24 00:00:00
abstract：:Although, the main physiological role of monocytes is attributed to innate immunity (that is, phagocytosis) and the development of tissue macrophages and dendritic cells, the pathophysiological role of these goes far behind these (simplistic) limits. Indeed, monocytes constitute a major source of blood tissue factor, ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH09-01-0023
更新日期：2009-11-01 00:00:00
abstract：:Sixty nine patients were treated with local intra-arterial urokinase (37,500 U/CTA. hr-1) for recent severe ischemia of lower limbs: 27 (40%) ultimately required amputation. The difference of amputation rate between the groups with and without thrombolysis was not significant (33% v. 42%). A biological study in 6 pati...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1981-06-30 00:00:00
abstract：:Thrombolytic therapy provides clinical benefit in patients with vascular occlusions, depending upon the organ or limb that is threatened. The impact of therapeutic intervention varies from the quiet alteration of the course of deep vein thrombosis, for which non-life threatening post-phlebitic syndrome can be largely ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1995-07-01 00:00:00
abstract：:The measurement of platelet deposition in human thrombi is essential for the evaluation of platelet-inhibitory drugs and prosthetic materials for use in patients. The rate of 111Indium-labelled platelet accumulation on Dacron arterial grafts was measured in 27 patients randomised to take either aspirin and dipyridamol...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1982-12-27 00:00:00
abstract：:Heparin and low-molecular-weight heparin (LMWH) are commonly monitored by determination of activated clotting times or chromogenic assays. Despite their wide use, these assays determine the biological activity and not the concentration of the anticoagulants. They may be inaccurate in some circumstances such as certain...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH09-03-0168
更新日期：2009-11-01 00:00:00
abstract：:Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in postmenopausal women via several mechanisms, including modifications in the fibrinolytic system and lipoprotein(a) [Lp(a)] levels. The aim of this study was to examine the influence of the levels and ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-01-01 00:00:00
abstract：:The emergency management of ST-elevation myocardial infarction (STEMI) involves treatment with dual-antiplatelet therapy (DAPT) and primary percutaneous coronary intervention (PPCI). Pain is generally treated with opiates, which may delay gastric transit and reduce DAPT absorption. We sought to assess the effect of mo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0038-1629896
更新日期：2018-03-01 00:00:00
abstract：:56 haemophiliacs selected on the basis of HIV-1 antibody status, liver disease grade and mean annual dose of clotting factor concentrate used were studied. Spontaneous and stimulated IgG and IgM production in vitro were measured. HIV-1 infection was associated with increased spontaneous immunoglobulin production and a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-01-23 00:00:00
abstract：:To investigate pituitary effects on the vitamin K-dependent coagulation factors, female rats were hypophysectomized (hypox) and treated with growth hormone (GH), cortisone, thyroxine, vitamin K, or saline. After 11 days of treatment, the prothrombin time, platelet count, and factors II, VII, IX, and X were determined....
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:Injection of human alpha 2-antiplasmin resulted in delayed elimination of fibrin from the lungs in rats with thrombin-induced intravascular coagulation. The amount of alpha 2-antiplasmin injected was chosen so as to simulate the posttraumatic increase of this inhibitor in man. By injecting trace amounts only of radiol...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1981-12-23 00:00:00
abstract：:The origin and evolution of venom toxins is a mystery that has evoked much interest. We have recently shown that pseutarin C, a prothrombin activator from Pseudonaja textilis venom, is structurally and functionally similar to mammalian coagulation factor Xa-factor Va complex. Its catalytic subunit is homologous to fac...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-11-0707
更新日期：2005-03-01 00:00:00
abstract：:Platelets are critically involved in atherosclerosis and acute thrombosis. The platelet phenotype shows a wide variability documented by the inherited difference of platelet reactivity, platelet volume and count and function of platelet surface receptors. Several candidate genes have been put into focus and investigat...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH13-02-0145
更新日期：2013-11-01 00:00:00
abstract：:CD36, also known as GPIIIb or GPIV, is a main protein of the platelet membrane. Accumulating evidence implicates CD36 in the pathogenesis of atherosclerosis. CD36 binds to cholesteryl-hemisuccinate coupled to agarose. This binding may be of physiologic relevance since CD36 has a long extracellular hydrophobic region a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:Causative mutations in the factor VIII gene of seven unrelated patients with severe haemophilia A were identified using the mutation screening procedure conformation sensitive gel electrophoresis (1) and characterised by direct sequencing. Female family members of all patients had requested either carrier status deter...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:We studied the occurrence of myocardial infarction (MI), ischaemic stroke (IS) and pulmonary embolism (PE) before and after breast cancer hospitalisation compared with cancer-free controls. For this, women with a first breast cancer hospitalisation during 2000-2007 were selected from the PHARMO Record Linkage System, ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH10-12-0778
更新日期：2011-07-01 00:00:00
abstract：:The esterase activity of highly purified human urokinase on Nalpha-acetylglycl-L-lysine methyl ester is strongly inhibited by 1 X 10(-5) to 1 X 10(-2)M Cu++, Hg++, Ni++, Co++, Fe+++, and Mn++ solutions, whereas Na+, K+, Ca++, and Mg++ are weakly effective. This inhibition is parallel with the inhibition of activation ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1978-02-28 00:00:00
abstract：:Normal adults have very few circulating endothelial cells (CECs) in their blood, but increased levels have been shown in association with conditions associated with endothelial damage such as myocardial infarction and stroke. As atrial fibrillation (AF) is associated with a hypercoagulable state and abnormalities of p...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH05-02-0093
更新日期：2005-10-01 00:00:00
abstract：:Heme oxygenase-1 (HO-1) decreases apoptosis, inflammation and oxidative stress. The aim of the study was to investigate the effects of intracoronary infusion of allogenic bone marrow cells (BMC) overexpressing HO-1 in the porcine model of myocardial infarction (MI). MI was produced by balloon occlusion of a coronary a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH12-05-0303
更新日期：2012-09-01 00:00:00
abstract：:The first step of coagulation factor XIII (FXIII) activation involves cleavage of the FXIII activation peptide (FXIII-AP) by thrombin. However, it is not known whether the FXIII-AP is released into plasma upon cleavage or remains attached to activated FXIII. The aim of the present work was to study the structure of fr...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-06-01 00:00:00
abstract：:Activated protein C (APC)-mediated inactivation of factor VIII (FVIII) correlates with cleavage at either Arg336 and/or Arg562. To elucidate the APC cleavage requirements for inactivation of FVIII, APC cleavage site mutants in FVIII (R336I, R562K and R336I/R562K) were made by site-directed mutagenesis. Analysis of the...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:Multiple clinical trials have proven that thrombolytic therapy is an effective treatment for acute myocardial infarction. Spontaneous intracranial hemorrhage (ICH) occurs in a small percentage of patients as a result of the treatment. The etiology of the ICH is unknown and there is currently no established experimenta...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:Vascular smooth muscle cell (VSMC) proliferation occurs in vascular obstructive events such as atherosclerosis and restenosis. We previously showed that Notch receptors are induced in smooth muscle cells during vascular remodeling. Our goal was to determine the mechanisms employed by Notch signaling to regulate prolif...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH06-04-0224
更新日期：2006-09-01 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：:Helicobacter pylori (H. pylori) infection is associated with peptic ulcer disease and gastric cancer. The eradication of H. pylori is of special interest in patients with congenital bleeding disorders, for whom treatment of gastrointestinal hemorrhage with factor concentrates is costly. The prevalence of H. pylori var...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-04-01 00:00:00
