Abstract:
:Secretion of platelet granules is necessary for normal hemostasis. Platelet secretion requires soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) complex formation between different members of the syntaxin, SNAP-25, and vesicle-associated membrane protein (VAMP) gene families. Using microcapillary reverse-phase high-performance liquid chromatography-nano-electrospray tandem mass spectrometry, we identified VAMP-3 and VAMP-8 as VAMP isoforms coimmunoprecipitated from platelets with syntaxin 4. Immunoblotting experiments confirmed the presence of VAMP-3 and VAMP-8 but not VAMP-1 or VAMP-2 in platelets. To examine the effect of VAMP proteins on platelet secretion, soluble recombinant (r) VAMP-2, rVAMP-3, and rVAMP-8 were incubated with streptolysin O-permeabilized platelets. Secretion of alpha granules (monitored by flow cytometric measurement of P-selectin) was blocked, and dense-granule secretion (assessed by release of carbon 14-serotonin) was almost completely inhibited by rVAMP-3, whereas rVAMP-8 inhibited secretion of dense granules but not alpha granules. In contrast, rVAMP-2, which formed SNARE complexes in vitro, had no effect on platelet exocytosis. We conclude that VAMP-3 and VAMP-8 form SNARE complexes with platelet syntaxin 4 and are required for platelet granule secretion.
journal_name
Bloodjournal_title
Bloodauthors
Polgár J,Chung SH,Reed GLdoi
10.1182/blood.v100.3.1081subject
Has Abstractpub_date
2002-08-01 00:00:00pages
1081-3issue
3eissn
0006-4971issn
1528-0020journal_volume
100pub_type
杂志文章相关文献
BLOOD文献大全abstract::Dendritic cells (DCs) are a key cell type in the initiation of the adaptive immune response. Recently, an additional role for DCs in suppressing myeloproliferation was discovered. Myeloproliferative disorder (MPD) was observed in murine studies with constitutive depletion of DCs, as well as in patients with congenital...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2018-05-850321
更新日期:2019-01-24 00:00:00
abstract::Hypoxia-inducible factor-1α (HIF1α), a master transcriptional regulator of the cellular and systemic hypoxia response, is essential for the maintenance of self-renewal capacity of normal HSCs. It is still unknown whether HIF1α has a role in survival regulation of leukemia stem cells (LSCs) in chronic myeloid leukemia ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-10-387381
更新日期:2012-03-15 00:00:00
abstract::The cell-surface expression of the MIC2 antigen defined by the monoclonal antibody 12E7 was investigated on human leukocytes in bone marrow (BM), thymus, and peripheral blood (PB) using multiparameter flow cytometry and cell sorting. In contrast to preceding reports, we found that the MIC2 antigen is not restricted to...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-01-15 00:00:00
abstract::Chronic granulomatous disease (CGD) is characterized by the absence of a respiratory burst in activated phagocytes. Defects in at least four different genes lead to CGD. Patients with the X-linked form of CGD have mutations in the gene for the beta-subunit of cytochrome b558 (gp91-phox). We studied the molecular defec...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-09-15 00:00:00
abstract::Aberrant activation of the Wnt pathway plays a pathogenetic role in various tumors and has been associated with adverse outcome in acute lymphoblastic leukemia (ALL). LEF1, a key mediator of Wnt signaling, has been linked to leukemic transformation, and recurrent mutations of LEF1 have been identified in pediatric T-A...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1182/blood-2011-04-350850
更新日期:2011-12-08 00:00:00
abstract::The ability of platelets to provide a highly reactive surface for the recruitment of other platelets and leukocytes to sites of vascular injury is critical for hemostasis, atherothrombosis, and a variety of inflammatory diseases. The mechanisms coordinating platelet-platelet and platelet-leukocyte interactions have be...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-08-040980
更新日期:2007-09-15 00:00:00
abstract::To date, all of the chromosomal deletions that cause alpha-thalassemia remove the structural alpha genes and/or their regulatory element (HS -40). A unique deletion occurs in a single family that juxtaposes a region that normally lies approximately 18-kilobase downstream of the human alpha cluster, next to a structura...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-08-01 00:00:00
abstract::Natural killer (NK) cells participate in host defense by surveying for and ultimately killing virally infected or malignant target cells. NK cell cytotoxicity is a tightly regulated process that proceeds stepwise from adhesion and activation to the secretion of preformed lytic granule contents onto a diseased or stres...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-06-437012
更新日期:2013-04-04 00:00:00
abstract::The platelet release reaction plays a critical role in thrombosis and contributes to the events that follow hemostasis. Previous studies have shown that platelet secretion is mediated by Soluble NSF Attachment Protein Receptor (SNARE) proteins from granule and plasma membranes. The SNAREs form transmembrane complexes ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-05-430603
更新日期:2012-09-20 00:00:00
abstract::Mixed-lineage leukemia (MLL)-AF4 fusion arises prenatally in high-risk infant acute pro-B-lymphoblastic leukemia (pro-B-ALL). In human embryonic stem cells (hESCs), MLL-AF4 skewed hematoendothelial specification but was insufficient for transformation, suggesting that additional oncogenic insults seem required for MLL...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-11-470146
更新日期:2013-05-09 00:00:00
abstract::The hematopoietically expressed homeobox gene, Hhex, is a transcription factor that is important for development of definitive hematopoietic stem cells (HSCs) and B cells, and that causes T-cell leukemia when overexpressed. Here, we have used an Hhex inducible knockout mouse model to study the role of Hhex in adult he...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-06-579813
更新日期:2015-01-29 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is suspected to be a strong mortality determinant of hemolytic disorders. However, direct contribution of acute intravascular hemolysis to fatal PAH has not been investigated. The roles of nitric oxide (NO) insufficiency and platelet activation in hemolysis-associated fatal PAH ha...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-01-267112
更新日期:2010-09-02 00:00:00
abstract::The genetic diversity of the human immunodeficiency virus (HIV) isolated from transfusion-associated AIDS patients has been examined. Restriction enzyme mapping studies of integrated proviral DNA of donor and recipient origin demonstrated genomic variation between isolates. Analysis of the molecularly cloned viral gen...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::To understand the etiology of bone modulation and hypercalcemia observed in granulocytosis of a tumor-bearing animal model and to gain insight into the implication of sustained hematopoietic stimulation on the bone tissue, in vivo responses of normal mouse hematopoietic and bone tissues to long-term injections of reco...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-05-15 00:00:00
abstract::Mammalian beta-globin loci are composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated. The expression of these genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HS...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract::We analyzed the incidence of posttransplant chronic myelogenous leukemia (CML) relapse in 283 consecutive related-donor (n = 177) and unrelated-donor (n = 106) allogeneic transplant recipients. Twenty-two of 165 related-donor recipients with stable or advanced disease at the time of transplant had hematologic relapse ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-07-15 00:00:00
abstract::In a prospective trial in 284 children with B-lineage acute lymphoblastic leukemia (ALL), we assessed the clinical utility of real-time quantitative polymerase chain reaction analysis of antigen receptor gene rearrangements for detection of minimal residual disease (MRD) to identify children at high risk of relapse. A...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2006-09-045369
更新日期:2007-09-01 00:00:00
abstract::Cumulative evidence indicates that MYC, one of the major downstream effectors of NOTCH1, is a critical component of T-cell acute lymphoblastic leukemia (T-ALL) oncogenesis and a potential candidate for targeted therapy. However, MYC is a complex oncogene, involving both fine protein dosage and cell-context dependency,...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-02-336842
更新日期:2011-06-16 00:00:00
abstract::Primary myelofibrosis (PMF) is the most serious myeloproliferative disorder, characterized by clonal myeloproliferation associated with cytokine-mediated bone marrow stromal reaction including fibrosis and osteosclerosis. Current drug therapy remains mainly palliative. Because the NF-kappaB pathway is implicated in th...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-10-054502
更新日期:2007-07-01 00:00:00
abstract::The putative chemokine receptor BLR1 has been identified as the first G-protein-coupled receptor involved in B-cell migration and in microenvironmental homing to B-cell follicles and to germinal centers. In healthy individuals, expression of BLR1 is restricted to all mature recirculating B cells and to a subpopulation...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-07-15 00:00:00
abstract::CTLA-4 is an inhibitory molecule that down-regulates T-cell activation. Although polymorphisms at CTLA-4 have been correlated with autoimmune diseases their association with clinical outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has yet to be explored. A total of 5 CTLA-4 single-nucleoti...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-01-069781
更新日期:2007-07-01 00:00:00
abstract::The nuclear factor-kappa B (NF-kappaB) gene transactivator serves in the formation of immune, inflammatory, and stress responses. In quiescent cells, NF-kappaB principally resides within the cytoplasm in association with inhibitory kappa (IkappaB) proteins. The status of IkappaB and NF-kappaB proteins was evaluated fo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::Selective depletion of the alloreactive T cells causing graft-versus-host disease (GVHD) without loss of the graft-versus-leukemia (GVL) effect is the holy grail of hematopoietic cell transplantation (HCT). In this issue of Blood, He et al demonstrate that inhibition of histone methylation leads to selective apoptosis...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2011-12-395905
更新日期:2012-02-02 00:00:00
abstract::In chronic lymphocytic leukemia (CLL) patients with mutated IGHV, 3 recent studies have demonstrated prolonged progression-free survival (PFS) after treatment with fludarabine-cyclophosphamide-rituximab (FCR) chemoimmunotherapy. We performed a systematic review to assess the benefit of FCR for patients with CLL and id...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2017-07-731588
更新日期:2017-11-23 00:00:00
abstract::The RUNX1/AML1 gene is the most frequently mutated gene in human leukemia. Conditional deletion of Runx1 in adult mice results in an increase of hematopoietic stem cells (HSCs), which serve as target cells for leukemia; however, Runx1(-/-) mice do not develop spontaneous leukemia. Here we show that maintenance of Runx...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-07-232249
更新日期:2010-02-25 00:00:00
abstract::The treatment of mice with high doses of 5-fluorouracil (5-FU) results in an enrichment of primitive hematopoietic progenitors. Using this procedure, we obtained a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro and could differentiate into not only myeloid cells b...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-07-15 00:00:00
abstract::A 13-yr-old Japanese female with acute lymphoblastic leukemia (ALL) that was associated with a Philadelphia chromosome (Ph1) as well as a 14q+ chromosome abnormality is reported. The cell surface phenotype of leukemic cells was determined to be non-T, non-B ALL on the basis of positive Ia-like antigen, terminal deoxyn...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-02-01 00:00:00
abstract::As a mediator of neurogenic inflammation and pain, we hypothesized that levels of the neuropeptide Substance P (SP) would be elevated in patients with sickle cell disease (SCD) with vaso-occlusive pain crisis. SP is a known stimulator of tumor necrosis factor-alpha (TNF-alpha) release and a promoter of interleukin-8 (...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-11-01 00:00:00
abstract::In ischemic stroke, treatment options are limited. Therapeutic thrombolysis is restricted to the first few hours after stroke, and the utility of current platelet aggregation inhibitors, including GPIIb/IIIa receptor antagonists, and anticoagulants is counterbalanced by the risk of intracerebral bleeding complications...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2008-04-144758
更新日期:2008-11-01 00:00:00
abstract::Therapeutic gene delivery to hematopoietic stem cells (HSCs) holds great potential as a life-saving treatment of monogenic, oncologic, and infectious diseases. However, clinical gene therapy is severely limited by intrinsic HSC resistance to modification with lentiviral vectors (LVs), thus requiring high doses or repe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019000040
更新日期:2019-10-17 00:00:00