Abstract:
:Collagen binding to glycoprotein VI (GPVI) induces signals critical for platelet activation in thrombosis. Both ligand-induced GPVI signaling through its coassociated Fc-receptor gamma-chain (FcRgamma) immunoreceptor tyrosine-activation motif (ITAM) and the calmodulin inhibitor, W7, dissociate calmodulin from GPVI and induce metalloproteinase-mediated GPVI ectodomain shedding. We investigated whether signaling by another ITAM-bearing receptor on platelets, FcgammaRIIa, also down-regulates GPVI expression. Agonists that signal through FcgammaRIIa, the mAbs VM58 or 14A2, potently induced GPVI shedding, inhibitable by the metalloproteinase inhibitor, GM6001. Unexpectedly, FcgammaRIIa also underwent rapid proteolysis in platelets treated with agonists for FcgammaRIIa (VM58/14A2) or GPVI/FcRgamma (the snake toxin, convulxin), generating an approximate 30-kDa fragment. Immunoprecipitation/pull-down experiments showed that FcgammaRIIa also bound calmodulin and W7 induced FcgammaRIIa cleavage. However, unlike GPVI, the approximate 30-kDa FcgammaRIIa fragment remained platelet associated, and proteolysis was unaffected by GM6001 but was inhibited by a membrane-permeable calpain inhibitor, E64d; consistent with this, micro-calpain cleaved an FcgammaRIIa tail-fusion protein at (222)Lys/(223)Ala and (230)Gly/(231)Arg, upstream of the ITAM domain. These findings suggest simultaneous activation of distinct extracellular (metalloproteinase-mediated) and intracellular (calpain-mediated) proteolytic pathways irreversibly inactivating platelet GPVI/FcRgamma and FcgammaRIIa, respectively. Activation of both pathways was observed with immunoglobulin from patients with heparin-induced thrombocytopenia (HIT), suggesting novel mechanisms for platelet dysfunction by FcgammaRIIa after immunologic insult.
journal_name
Bloodjournal_title
Bloodauthors
Gardiner EE,Karunakaran D,Arthur JF,Mu FT,Powell MS,Baker RI,Hogarth PM,Kahn ML,Andrews RK,Berndt MCdoi
10.1182/blood-2007-04-086983subject
Has Abstractpub_date
2008-01-01 00:00:00pages
165-74issue
1eissn
0006-4971issn
1528-0020pii
blood-2007-04-086983journal_volume
111pub_type
杂志文章相关文献
BLOOD文献大全abstract::The anti-CD33 antibody calicheamicinconjugate gemtuzumab ozogamicin (GO) was used to treat 16 patients with acute promyelocytic leukemia (APL) who had relapsed at the molecular level. Of these patients, 8 were experiencing a first, 5 a second, 2 a third, and 1 a fourth relapse. GO was administered at 6 mg/m2 for 2 dos...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2004-04-1550
更新日期:2004-10-01 00:00:00
abstract::Human immunodeficiency virus-1 (HIV-1)-Tat, the transactivating gene product of HIV-1, has been shown to interact with different cell types, inducing gene expression, altering their growth and migratory behavior. In this study we examined whether Tat might affect functions of acquired immunodeficiency syndrome (AIDS)-...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::Germ-line GATA2 gene mutations, leading to haploinsufficiency, have been identified in patients with familial myelodysplastic syndrome/acute myeloid leukemia, monocytopenia and mycobacterial infections, Emberger syndrome, and dendritic cell, monocyte, B-, and NK-cell deficiency. GATA2 mutations have also been reported...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-06-580340
更新日期:2015-01-01 00:00:00
abstract::Between 1990 and 1996, we conducted a randomized trial in adults with newly diagnosed acute myeloid leukemia (AML) in order to compare relapse-free interval (RFI) after double induction (arm B), timed-sequential induction (arm C), or control "3 + 7" induction (arm A). Patients achieving complete remission (CR) after i...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1182/blood-2003-10-3561
更新日期:2004-10-15 00:00:00
abstract::We have examined the effects of administration of stem cell-factor (SCF) on the number and distribution of pluripotent hematopoietic stem cells (PHSC) in normal mice. Using the competitive repopulation assay we found that in vivo administration of SCF increases the absolute number of PHSC per mouse threefold. The incr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-07-15 00:00:00
abstract::Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation an...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
abstract::To identify molecular targets that modify sensitivity to lenalidomide, we measured proliferation in multiple myeloma (MM) cells transfected with 27 968 small interfering RNAs in the presence of increasing concentrations of drug and identified 63 genes that enhance activity of lenalidomide upon silencing. Ribosomal pro...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-05-577130
更新日期:2015-01-15 00:00:00
abstract::To know the role and initiation mechanism of the interaction of glycoprotein (GP) Ib with surface-immobilized von Willebrand factor (vWF), we examined the effect of shear stress levels on platelet binding to vWF-coated plates using a cone-and-plate type viscometer capable of loading various levels of shear stress. The...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-11-15 00:00:00
abstract::Quantitative studies of bone marrow neutrophil pool sizes and production rates and of blood neutrophil kinetics were performed in 16 patients with chronic neutropenia without splenomegaly. Marrow netrophil cellularity was determined from a ferrokinetic estimate of marrow normoblasts and from neutrophil-erythroid ratio...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1979-09-01 00:00:00
abstract::Expression of B7 family costimulatory molecules on B cells defines their capacity to function as antigen presenting cells (APCs). B cells that do not express B7 costimulatory molecules induce T-cell tolerance. Therefore, the expression of B7 costimulatory molecules on malignant B cells might be critical for their reco...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract::High efficiency retroviral-mediated gene transfer to rhesus CD4+ peripheral blood lymphocytes (PBL) was accomplished using an optimized transduction protocol using a gibbon ape leukemia virus (GaLV) envelope-containing packaging cell line PG13. Engineered CD4+ PBL were administered to three nonmyeloablated animals in ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-03-15 00:00:00
abstract::Vascular bypass procedures in the central nervous system (CNS) remain technically challenging, hindered by complications and often failing to prevent adverse outcome such as stroke. Thus, there is an unmet clinical need for a safe and effective CNS revascularization. Vascular endothelial growth factors (VEGFs) are pro...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-07-441527
更新日期:2013-08-01 00:00:00
abstract::Characterization of lymphocytes including B cells during early versus chronic HIV infection is important for understanding the impact of chronic viremia on immune cell function. In this setting, we investigated B cells before and after reduction of HIV plasma viremia by antiretroviral therapy (ART). At baseline, perip...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-285528
更新日期:2010-12-16 00:00:00
abstract::T-cell depletion (TCD) of the donor marrow graft has been shown to reduce the severity of graft-versus-host disease (GVHD) in patients with chronic-phase (CP) chronic myelogenous leukemia (CML) undergoing HLA-identical sibling allogeneic marrow transplantation. However, there has been a corresponding reduction in the ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-07-15 00:00:00
abstract::Conditioned medium (CM) obtained from a human hepatoma cell line, SK-HEP-1, contains colony-stimulating factors (CSFs) active on murine and human bone marrow-derived granulocyte and macrophage colony-forming units (CFU-GM) and a factor capable of inducing granulocyte-macrophage differentiation (GM-DF) of murine myelom...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-08-01 00:00:00
abstract::During an 8-year period, 3,638 children from institutions of the Pediatric Oncology Group (POG) were diagnosed with acute lymphoblastic leukemia (ALL). Fifty-seven patients had Philadelphia chromosome-positive (Ph1) ALL. Blast cells obtained at diagnosis from 13 of these 57 cases (23%) were also found to have partial ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract::The tal-1 gene encodes a basic helix-loop-helix (bHLH) transcription factor required for primitive and definitive hematopoiesis. Additionally, ectopic activation of the tal-1 gene during T lymphopoiesis occurs in numerous cases of human T-cell acute lymphoblastic leukemia. With the use of transgenic mice, we show that...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v100.2.491
更新日期:2002-07-15 00:00:00
abstract::Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation....
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::The coagulation factors V (FV) and VIII (FVIII) are important at sites of vascular injury for the amplification of the clotting cascade. Natural variants of these factors frequently lead to severe bleeding disorders. To understand the mechanisms of activation of FVIII by thrombin, we used a bank of mutant thrombins to...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-03-0843
更新日期:2002-10-15 00:00:00
abstract::Severe elevation of red blood cell number is often associated with hypertension and thromboembolism resulting in severe cardiovascular complications. However, some individuals such as high altitude dwellers cope well with an increased hematocrit level. We analyzed adaptive mechanisms to excessive erythrocytosis in our...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-01-0283
更新日期:2003-09-15 00:00:00
abstract::Mast cells accumulate at sites of neovascularization, solid tumors, and many immune reactions. Such accumulation requires directed migration of mature mast cells or their precursors. The nature of the chemoattractants that regulate mast cell motility and the identity of the receptors that mediate the chemotactic respo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-02-15 00:00:00
abstract::The BCR-ABL1 fusion kinase is frequently associated with chronic myeloid leukemia and B-cell acute lymphoblastic leukemia but is rare in T-cell acute lymphoblastic leukemia (T-ALL). We recently identified NUP214-ABL1 as a variant ABL1 fusion gene in 6% of T-ALL patients. Here we describe the identification of another ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-12-4897
更新日期:2005-06-15 00:00:00
abstract::We evaluated the efficacy of umbilical cord blood (UCB) in the setting of a nonmyeloablative regimen consisting of fludarabine (200 mg/m2), cyclophosphamide (50 mg/kg), and a single fraction of total body irradiation (200 cGy) with cyclosporine and mycophenolate mofetil for posttransplantation immunoprophylaxis. The t...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2007-04-067215
更新日期:2007-10-15 00:00:00
abstract::Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-03-703819
更新日期:2016-08-25 00:00:00
abstract::Marrow specimens obtained from 23 patients with acute myelocytic leukemia were exposed to cytosine arabinoside and/or daunorubicin in vitro, and the effects of these agents on colony formation in vitro was determined. Thymidine suicide indices were determined as well, which permitted a distinction to be made between k...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-09-01 00:00:00
abstract::The proto-oncogene c-fos was transiently upregulated in primitive hematopoietic stem (Lin-Sca-1(+)) cells stimulated with stem cell factor, interleukin-3 (IL-3), and IL-6. To investigate a role of the c-fos in hematopoietic stem cells, we used bone marrow (BM) cells from transgenic mice carrying the c-fos gene under t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00
abstract::Eleven of twenty-four patients with severe aplastic anemia given marrow grafts from HLA-identical siblings between October 1970 and March 1973 are alive with normal marrow function and continued evidence of engraftment 3-5 yr later. Ten have been leading normal lives with no immunosuppressive or other drug therapy sin...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
abstract::Pim kinases are involved in B-cell development and are overexpressed in B-cell chronic lymphocytic leukemia (CLL). We hypothesized that Pim kinase inhibition would affect B-cell survival. Identified from a screen of imidazo[1,2-b]pyridazine compounds, SGI-1776 inhibits Pim-1, Pim-2, and Pim-3. Treatment of CLL cells w...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-03-212852
更新日期:2009-11-05 00:00:00
abstract::Nitric oxide is a short-lived reactive mediator that inhibits bone marrow (BM) cell proliferation induced by granulocyte-macrophage colony-stimulating factor (GM-CSF). The present studies show that nitric oxide also inhibits macrophage colony-stimulating factor (M-CSF)-induced growth of mouse BM cells, an effect that ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::Macrophages infiltrating solid tumors exhibit a tumor-supporting phenotype and are critical for tumor development. Little is known which tumor-derived signal provokes this phenotype shift and how these signals are interpreted in macrophages to support tumor growth. We used the supernatant of apoptotic cells and notice...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-01-201889
更新日期:2009-09-03 00:00:00