Abstract:
:Transforming growth factor-beta1 (TGF-beta1) has potent physiologic and pathologic effects on a variety of cell types at subnanomolar concentrations. Platelets contain 40 times as much TGF-beta1 as other cells and secrete it as an inactive (latent) form in complex with latency-associated peptide (LAP), which is disulfide bonded via Cys33 to latent TGF-beta binding protein 1 (LTBP-1). Little is known about how latent TGF-beta1 becomes activated in vivo. Here we show that TGF-beta1 released from platelets or fibroblasts undergoes dramatic activation when subjected to stirring or shear forces, providing a potential mechanism for physiologic control. Thiol-disulfide exchange appears to contribute to the process based on the effects of thiol-reactive reagents and differences in thiol labeling of TGF-beta1 before and after stirring or shear. Activation required the presence of LTBP, as TGF-beta1 contained in complex with only LAP could not be activated by stirring when studied as either a recombinant purified protein complex or in the platelet releasates or sera of mice engineered to contain an LAP C33S mutation. Release and activation of latent TGF-beta1 in vivo was demonstrated in a mouse model 5 minutes after thrombus formation. These data potentially provide a novel mechanism for in vivo activation of TGF-beta1.
journal_name
Bloodjournal_title
Bloodauthors
Ahamed J,Burg N,Yoshinaga K,Janczak CA,Rifkin DB,Coller BSdoi
10.1182/blood-2008-04-151753subject
Has Abstractpub_date
2008-11-01 00:00:00pages
3650-60issue
9eissn
0006-4971issn
1528-0020pii
blood-2008-04-151753journal_volume
112pub_type
杂志文章相关文献
BLOOD文献大全abstract::Various virus infections cause dysfunctional hemostasis and in some instances lead to the development of viral hemorrhagic fever syndrome. How do diverse viruses induce the expression of tissue factor on vascular cells? We hypothesize that a direct stimulation of pattern recognition receptors (PRR) by viral nucleic ac...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-02-137901
更新日期:2009-01-15 00:00:00
abstract::Ectopic expression of the erythropoietin receptor (EpoR) in the interleukin-3 (IL-3)-dependent cell line Ba/F3 results in growth and partial erythroid differentiation in Epo. In contrast, introduction and activation of the interleukin-5 receptor (IL-5R) or of the granulocyte-macrophage colony-stimulating factor recept...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
abstract::Approximately 20% of children with acute lymphoblastic leukemia (ALL) relapse because of failure to eradicate the disease. Current drug efficacy studies focus on reducing leukemia cell burden. However, if drugs have limited effects on leukemia-initiating cells (LICs), then these cells may expand and eventually cause r...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-08-448852
更新日期:2013-02-21 00:00:00
abstract::We evaluated the ability of 2 human mAbs directed against TRAILR1 (HGS-ETR1) and TRAILR2 (HGS-ETR2) to kill human myeloma cells. HGS-ETR1 and HGS-ETR2 mAbs killed 15 and 9 human myeloma cell lines (HMCLs; n = 22), respectively. IL-6, the major survival and growth factor for these HMCLs, did not prevent their killing. ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-12-007971
更新日期:2006-08-15 00:00:00
abstract::Histone deacetylase 6 (HDAC6) is a heat shock protein 90 (hsp90) deacetylase. Treatment with pan-HDAC inhibitors or depletion of HDAC6 by siRNA induces hyperacetylation and inhibits ATP binding and chaperone function of hsp90. Treatment with 17-allylamino-demothoxy geldanamycin (17-AAG) also inhibits ATP binding and c...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-03-143644
更新日期:2008-09-01 00:00:00
abstract::In this study, we examined in detail the interaction of platelet factor-4 (PF-4) with fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) and the effect of PF-4-derived synthetic peptides. We show that a peptide between amino acids 47 and 70 that contains the heparin-binding lysine-rich si...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-08-01 00:00:00
abstract::Leukocyte transendothelial migration (TEM) is a critical event during inflammation. CD47 has been implicated in myeloid cell migration across endothelium and epithelium. CD47 binds to signal regulatory protein (SIRP), SIRPalpha and SIRPgamma. So far, little is known about the role of endothelial CD47 in T-cell TEM in ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-01-134429
更新日期:2008-08-15 00:00:00
abstract::To obtain insight into the mechanism(s) of posttransplantation humoral immunodeficiency, we evaluated factors affecting serum antibody levels against polio, tetanus, Haemophilus influenzae, and Streptococcus pneumoniae in 87 patients. Patients with hematologic malignancies were randomized to receive marrow versus bloo...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1182/blood-2002-05-1376
更新日期:2003-04-15 00:00:00
abstract::Intravenous immunoglobulin (IVIgG) causes an acute rise in the platelet count in the majority of patients with chronic immune thrombocytopenic purpura (ITP) but the mechanism(s) of action is still unknown. We evaluated the ability of three different IVIgG preparations to inhibit the in vitro binding of autoantibody to...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-11-15 00:00:00
abstract::The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; c...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.11.3628
更新日期:2001-06-01 00:00:00
abstract::Pneumonia induced by Gram-negative bacteria is a common and serious disease associated with high morbidity and mortality. Elimination of bacterial pathogens relies on the recruitment and functions of neutrophils. The adhesion molecule L-selectin has recently been implicated in integrin activation in neutrophils (insid...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019000685
更新日期:2019-10-24 00:00:00
abstract::Deferoxamine (DFO) is a high-affinity Fe (III) chelator produced by Streptomyces pilosus. DFO is used clinically to remove iron from patients with iron overload disorders. Orally administered DFO cannot be absorbed, and therefore it must be injected. Here we show that DFO induces ferritin degradation in lysosomes thro...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-05-224188
更新日期:2009-11-12 00:00:00
abstract::CCR5 is a receptor for several beta chemokines and the entry coreceptor used by macrophage-tropic (R5) strains of HIV-1. In addition to supporting viral entry, CCR5 ligation by the HIV-1 envelope glycoprotein 120 (gp120) can activate intracellular signals in macrophages and trigger inflammatory mediator release. Using...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-12-012815
更新日期:2006-08-15 00:00:00
abstract::Blood cells of an adult vertebrate are continuously generated by hematopoietic stem cells (HSCs) that originate during embryonic life within the aorta-gonad-mesonephros region. There is now compelling in vivo evidence that HSCs are generated from aortic endothelial cells and that this process is critically regulated b...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-01-264382
更新日期:2010-08-12 00:00:00
abstract::Heparin is a widely used anticoagulant. Because of its negative charge, it forms complexes with positively charged platelet factor 4 (PF4). This can induce anti-PF4/heparin IgG Abs. Resulting immune complexes activate platelets, leading to the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT)....
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-05-353391
更新日期:2012-02-02 00:00:00
abstract::Human herpesvirus 6 activity (HHV-6) was studied in 15 allogeneic and 11 autologous marrow transplantation patients. After transplantation, HHV-6 was isolated from the peripheral blood mononuclear cells of 12 of 26 patients (6 allogeneic and 6 autologous). All isolates were variant B. Eleven of 26 and 12 of 19 patient...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-06-15 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::The proteolytic cleavage and subsequent inactivation of recombinant human factor VIII (rhFVIII) and human factor VIIIa (rhFVIIIa) by recombinant human activated protein C (rAPC) was analyzed in the presence and absence of human protein S and human factor V (FV). Membrane-bound rhFVIIIa spontaneously looses most of its...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::Two kinds of erythrocytes are released in the blood of irradiated adult hybrid mice grafted with parental fetal liver cells: fetal antigen-bearing erythrocytes (Ft+ cells) and adult-type Ft- erythrocytes. Both are of parental origin, as determined by immune lysis using histocompatibility alloantigens. The latter cells...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00
abstract::Drug-induced immune thrombocytopenia (DITP) is an adverse drug effect mediated by drug-dependent antibodies. Intravenous immunoglobulin (IVIG) is frequently used to treat DITP and primary immune thrombocytopenia (ITP). Despite IVIG's proven beneficial effects in ITP, its efficacy in DITP is unclear. We have establishe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-02-268326
更新日期:2010-09-16 00:00:00
abstract::Some Ki-1 lymphomas carry a specific chromosomal translocation, t(2;5)(p23;q35). We have recently found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in a human Ki-1 lymphoma with this translocation. Subsequent cDNA cloning showed that p80 is a fusion protein of two different genes on chromosome 2p23...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Human erythroid alpha-spectrin alleles responsible for hereditary elliptocytosis (alphaHE alleles) undergo increased incorporation into red blood cell membranes when the polymorphism alphaLELY (LELY: Low Expression LYon) occurs in trans. The alphaLELY polymorphism is characterized by a mutation in exon 40 at codon 185...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-11-15 00:00:00
abstract::Antibody-mediated pure red cell aplasia is a rare but serious event resulting from the induction of neutralizing erythropoietin (Epo)-specific antibodies provoked by treatment with recombinant Epo. Because of the crucial role of CD4 T cells in humoral response, we have quantified the number of Epo-specific CD4 T cells...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-04-280875
更新日期:2010-11-25 00:00:00
abstract::The bcr-abl chimeric messenger RNA is frequently detected in chronic myeloid leukemia (CML) patients after bone marrow transplantation. It was previously reported that the relapse risk of bcr-abl detection 6 to 12 months after transplantation was greater than 40%. This risk decreased as the time between transplantatio...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood.v98.6.1701
更新日期:2001-09-15 00:00:00
abstract::During the course of multiple myeloma (MM), new monoclonal proteins of an isotype distinct from the original clone, referred to as secondary monoclonal gammopathy of undetermined significance (MGUS), have been described. We report on the frequency, characteristics, and outcome of secondary MGUS. Of the 1942 patients w...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-04-349175
更新日期:2011-09-15 00:00:00
abstract::Chromosome 7 translocations, deletions, or monosomy are associated with myelodysplasia (MDS) and acute myeloid leukemia both in children and adults. These chromosomal anomalies represent one of the most common cytogenetic abnormalities associated with these diseases and usually herald a poor prognosis. In this study t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Apoptotic cells were shown to induce dendritic cell immune tolerance. We applied a proteomic approach to identify molecules that are secreted from apoptotic monocytes, and thus may mediate engulfment and immune suppression. Supernatants of monocytes undergoing apoptosis were collected and compared using sodium dodecyl...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-03-013334
更新日期:2006-11-15 00:00:00
abstract::The purpose of this study was to compare transplantation outcomes in patients with hematologic malignancies who received marrow grafts from either phenotypically matched unrelated, one-antigen-mismatched unrelated, or highly human leukocyte antigen (HLA)-disparate family donors. Between 1993 and 2000, 139 patients und...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.3.806
更新日期:2002-02-01 00:00:00
abstract::Granulocyte colony-stimulating factor (G-CSF) is essential for the host response to bacterial infection by controlling neutrophil production in the bone marrow. The G-CSF receptor (G-CSFR) activates the Jak/STAT pathway, although little is understood about how these signals regulate basal and stress-induced granulopoi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-02-003012
更新日期:2006-12-01 00:00:00
abstract::Dendritic cells (DCs) are professional antigen-presenting cells that are highly effective adjuvants for immunizing against pathogens and tumor antigens. The potential merit of genetic approaches to loading DCs with antigens is to express high and sustained levels of proteins that can be subsequently processed and pres...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.1.114
更新日期:2001-01-01 00:00:00