Abstract:
:Plasminogen activation rates are enhanced by cell surface binding. We previously demonstrated that exogenous plasminogen binds to phosphatidylserine-exposing and spread platelets. Platelets contain plasminogen in their α-granules, but secretion of plasminogen from platelets has not been studied. Recently, a novel transmembrane lysine-dependent plasminogen receptor, Plg-RKT, has been described on macrophages. Here, we analyzed the pool of plasminogen in platelets and examined whether platelets express Plg-RKT. Plasminogen content of the supernatant of resting and collagen/thrombin-stimulated platelets was similar. Pretreatment with the lysine analog, ε-aminocaproic acid, significantly increased platelet-derived plasminogen (0.33 vs 0.08 nmol/108 platelets) in the stimulated supernatant, indicating a lysine-dependent mechanism of membrane retention. Lysine-dependent, platelet-derived plasminogen retention on thrombin and convulxin activated human platelets was confirmed by flow cytometry. Platelets initiated fibrinolytic activity in fluorescently labeled plasminogen-deficient clots and in turbidimetric clot lysis assays. A 17-kDa band, consistent with Plg-RKT, was detected in the platelet membrane fraction by western blotting. Confocal microscopy of stimulated platelets revealed Plg-RKT colocalized with platelet-derived plasminogen on the activated platelet membrane. Plasminogen exposure was significantly attenuated in thrombin- and convulxin-stimulated platelets from Plg-RKT-/- mice compared with Plg-RKT+/+ littermates. Membrane exposure of Plg-RKT was not dependent on plasminogen, as similar levels of the receptor were detected in plasminogen-/- platelets. These data highlight Plg-RKT as a novel plasminogen receptor in human and murine platelets. We show for the first time that platelet-derived plasminogen is retained on the activated platelet membrane and drives local fibrinolysis by enhancing cell surface-mediated plasminogen activation.
journal_name
Bloodjournal_title
Bloodauthors
Whyte CS,Morrow GB,Baik N,Booth NA,Jalal MM,Parmer RJ,Miles LA,Mutch NJdoi
10.1182/blood.2020007263subject
Has Abstractpub_date
2021-01-14 00:00:00pages
248-257issue
2eissn
0006-4971issn
1528-0020pii
463466journal_volume
137pub_type
杂志文章相关文献
BLOOD文献大全abstract::The spread of multiple myeloma (MM) involves (re)circulation into the peripheral blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote metastasis through activation of proteins involved in the epithelial-mesenchymal transition (EMT) process. We hypothesized...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-09-380410
更新日期:2012-06-14 00:00:00
abstract::The activities of four purified human growth factors: biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor (GM-CSF); recombinant erythroid-potentiating activity (EPA); natural and recombinant pluripoietin (Ppo); and natural pluripoietin alpha (Ppo alpha), were compared on the growth of hematopoi...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract::Families with 3 different syndromes characterized by autosomal dominant inheritance of low platelet count and giant platelets were studied. Fechtner syndrome is an autosomal-dominant variant of Alport syndrome manifested by nephritis, sensorineural hearing loss, and cataract formation in addition to macrothrombocytope...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-11-15 00:00:00
abstract::Mutations that produce glucose-6-phosphate dehydrogenase (G6PD) deficiency have been identified in samples from patients with hemolytic disease in the United States, and in G6PD-deficient samples from Greece, the Canary Islands, the Czech and Slovak Republics, South China, and in samples from the Coriell Cell Reposito...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increas...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-03-15 00:00:00
abstract::Fetal/neonatal immune responses generally are considered to be immature and weaker than that of adults. We have studied the cord-blood T cells of newborns congenitally infected with Trypanosoma cruzi, the protozoan agent of Chagas disease. Our data demonstrate a predominant activation of CD8 T cells expressing activat...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2002-09-15 00:00:00
abstract::The mammalian target of rapamycin (mTOR) plays crucial roles in proliferative and antiapoptotic signaling in lymphoid malignancies. Rapamycin analogs, which are allosteric mTOR complex 1 (mTORC1) inhibitors, are active in mantle cell lymphoma and other lymphoid neoplasms, but responses are usually partial and short-li...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-04-346601
更新日期:2012-01-12 00:00:00
abstract::Studying human antigen-specific memory B cells has been challenging because of low frequencies in peripheral blood, slow proliferation, and lack of antibody secretion. Therefore, most studies have relied on conversion of memory B cells into antibody-secreting cells by in vitro culture. To facilitate direct ex vivo iso...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-03-341917
更新日期:2011-07-14 00:00:00
abstract::Myelodysplastic and leukemic stem cell clones that evolve in children and adults with Fanconi anemia universally bear complex cytogenetic abnormalities. The abnormalities are generally recurring deletions or chromosomal loss and involve precisely the same chromosomes with the same frequency as has been described in ma...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-09-2781
更新日期:2003-07-01 00:00:00
abstract::We used the polymerase chain reaction (PCR) to detect ALL1-AF4 rearrangements, the molecular hallmark of t(4;11) in a series of 46 pre-pre-B (CD19+, CD24+, CD10/CD20/cylgM/sIgM-) acute lymphoblastic leukemias (ALL). Eighteen patients (39%) exhibited fusion transcripts including 4 of 12 children and 14 of 34 adults. Th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Clinical and cytogenetic findings in 10 patients with deletions of the long arm of chromosomes 5 (5q-) are reported. Five cases had refractory anemia, the preleukemic syndrome, or refractory anemia with an excess of blasts; in all but one, the 5q- was the single initial abnormality. Three patients had overt leukemia; ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract::MRP8 and MRP14 are two S100-like calcium-binding proteins of unknown function, associated with numbers of human inflammatory disorders. Both molecules have been described as L1 complex, cystic fibrosis antigen, or p8 and p14. We report here the cloning of mouse MRP8 and MRP14 and their pattern of expression during hem...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-04-15 00:00:00
abstract::The duration of immunodeficiency following marrow transplantation is not known. Questionnaires were used to study the infection rates in 72 patients surviving 20 to 30 years after marrow grafting. Furthermore, in 33 of the 72 patients and in 16 donors (siblings who originally donated the marrow) leukocyte subsets were...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.13.3505
更新日期:2001-12-15 00:00:00
abstract::The receptors for interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are heterodimers comprised of ligand specific alpha chains and a common beta chain. The genes encoding the IL-5 receptor alpha chain and the common beta chain reside on chromosome 3 and 22 respectively, while th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::In this issue of Blood, White et al provide compelling evidence that the intrinsic apoptotic caspase cascade, while required for megakaryocyte and platelet death under pathophysiologic conditions, is dispensable for normal platelet formation and function. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2012-02-410423
更新日期:2012-05-03 00:00:00
abstract::The LAZ3 gene encodes a novel zinc-finger protein that shares homology with several Drosophila transcription factors. This gene was identified by its disruption in translocations involving chromosome 3q27 in diffuse large-cell lymphomas. To assess the frequency and role of this gene's involvement in lymphomagenesis an...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-05-15 00:00:00
abstract::To evaluate the association between fetal hemoglobin (HbF) levels and morbidity in β-thalassemia intermedia (TI), we analyzed data from 63 untransfused patients who had also never received HbF induction therapy. Patient records were reviewed for any history of 10 predefined morbidities. Laboratory measurements for mar...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2011-09-382408
更新日期:2012-01-12 00:00:00
abstract::Although thrombin is a key enzyme in the coagulation cascade and is required for both normal hemostasis and pathologic thrombogenesis, it also participates in its own negative feedback via activation of protein C, which downregulates thrombin generation by enzymatically inactivating factors Va and VIIIa. Our group and...
journal_title:Blood
pub_type: 杂志文章,随机对照试验
doi:10.1182/blood.2019002771
更新日期:2020-02-27 00:00:00
abstract::Platelet von Willebrand factor (vWF) has been suggested to play an important role in the hemostatic process. Clinical and experimental data indicate that bleeding time (BT) and platelet-vessel wall interaction cannot be normalized unless the defect of platelet vWF is also corrected. We have examined the effect of norm...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::The POEMS syndrome is associated with elevated vascular endothelial growth factor (VEGF) levels. Several studies have compared serum VEGF levels between POEMS patients and other disease entities showing higher serum VEGF in POEMS syndrome; however, it is unknown whether serum levels are reliable and reproducible given...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-06-362392
更新日期:2011-10-27 00:00:00
abstract::The anti-CD20 monoclonal antibody (mAb) rituximab has revolutionized the treatment of B-cell malignancies. This unprecedented success has not only substantially changed the mindset of the clinical community about the ability of mAb to improve outcomes but has catalyzed the interest in the pharmaceutical industry to de...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-07-298356
更新日期:2011-03-17 00:00:00
abstract::Small cell lung cancer is distinguished from other lung cancer histologic types by possessing a variety of neuroendocrine properties. Anti-Leu-7 is a monoclonal antibody that recognizes a 110,000-dalton molecular weight glycoprotein initially described on natural killer cells and subsequently reported on a variety of ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::Mitochondrial clearance is a well recognized but poorly understood biologic process, and reticulocytes, which undergo programmed mitochondrial clearance, provide a useful model to study this phenomenon. At the ultrastructural level, mitochondrial clearance resembles an autophagy-related process; however, the role of a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-04-151639
更新日期:2009-07-02 00:00:00
abstract::Prevention of erythrocyte dehydration is a potential therapeutic strategy for sickle cell disease. Increasing erythrocyte magnesium (Mg) could inhibit sickle cell dehydration by increasing chloride (CI) and water content and by inhibiting potassium chloride (K-CI) cotransport. In transgenic SAD 1 and (control) C57BL/6...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::In previous experimental animal studies it has been demonstrated that antibody depletion is not followed by increased antibody synthesis. To assess whether these results are conferrable to antibody-depleted humans, we measured free light chains (flcs) as markers of current antibody synthesis in 8 patients treated with...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-01-0128
更新日期:2002-07-01 00:00:00
abstract::Using a cohort of C57BL/6 (B6) x (NZB x B6)F1 backcross male mice bearing the Yaa (Y-linked autoimmune acceleration) mutation, we mapped and characterized the NZB-derived susceptibility loci predisposing to the development of autoimmune hemolytic anemia (AHA). Our analysis identified 2 major loci on NZB chromosome 7 a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-02-0558
更新日期:2005-08-15 00:00:00
abstract::p27 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating G(1)/S progression, and whose activity is, in part, regulated through interactions with D-type cyclins. Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation resulting in deregulated cyclin D1. We previously showed ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-01-0263
更新日期:2003-04-15 00:00:00
abstract::Control of intensity and duration of erythropoietin (Epo) signaling is necessary to tightly regulate red blood cell production. We have recently shown that the ubiquitin/proteasome system plays a major role in the control of Epo-R signaling. Indeed, after Epo stimulation, Epo-R is ubiquitinated and its intracellular p...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-10-055350
更新日期:2007-06-15 00:00:00
abstract::Incubation of normal human plasma with dextran sulfate for 7 min at 4 degrees C generates kallikrein amidolytic activity. No kallikrein activity is generated in factor XII or prekallikrein-deficient plasma and only small amounts (8%) in high molecular weight (HMW) kininogen-deficient plasma. Addition of specific antis...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-06-01 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