Abstract:
:Catabolism of free heme by heme oxygenase-1 (HO-1) generates carbon monoxide, biliverdin, and free iron (Fe). These end-products are responsible for much of the biologic activity of HO-1, including anti-inflammatory, antiapo-ptotic, antiproliferative, and antioxidant effects. We have identified an additional cytoprotective action, the regulation of complement activation, mediated via induction of decay-accelerating factor (DAF). Pharmacologic inhibition or short-interfering RNA (siRNA) depletion of HO-1 prevented induction of DAF expression in human endothelial cells. In contrast, HO-1 agonists hemin and cobalt protoporphyrin IX significantly increased DAF protein expression, reflecting an increase in transcription and steady-state mRNA. Adenoviral-mediated overexpression of HO-1 increased DAF expression, enhancing protection against C3 deposition and complement-mediated lysis, and this was reversed by DAF inhibitory monoclonal antibody (mAb) 1H4. Likewise, bilirubin, Fe chelation, and overexpression of heavy-chain ferritin all induced DAF expression in endothelial cells (EC). Analysis of cardiac endothelial cells isolated from Hmox1(-/-) mice revealed a 60% reduction in DAF expression compared with Hmox1(+/+) EC, and Hmox1(-/-) cells showed enhanced sensitivity to complement. We propose that modulation of complement activation through induction of DAF represents an important component of the cytoprotective effects of HO-1 against vascular injury, such as that associated with posttransplant vasculopathy, allograft rejection, and ischemia reperfusion.
journal_name
Bloodjournal_title
Bloodauthors
Kinderlerer AR,Pombo Gregoire I,Hamdulay SS,Ali F,Steinberg R,Silva G,Ali N,Wang B,Haskard DO,Soares MP,Mason JCdoi
10.1182/blood-2008-04-152934subject
Has Abstractpub_date
2009-02-12 00:00:00pages
1598-607issue
7eissn
0006-4971issn
1528-0020pii
blood-2008-04-152934journal_volume
113pub_type
杂志文章相关文献
BLOOD文献大全abstract::The expression of a number of blood coagulation factors (F) (FX, FIX, FVIII, FVII, alpha-, beta-, gamma-fibrinogen chains, protein C, and antithrombin III [AT III]) was analyzed at RNA and protein level in 5- to 10-week-old human embryos and fetuses. FX, FIX, and FVII were also analyzed at protein level. Total and pol...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-09-15 00:00:00
abstract::BRCA1 is critical for maintenance of genomic stability and interacts directly with several proteins that regulate hematopoietic stem cell function and are part of the Fanconi anemia (FA) double-strand break DNA repair pathway. The effects of complete BRCA1 deficiency on bone marrow (BM) function are unknown. To test t...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-03-635599
更新日期:2016-01-21 00:00:00
abstract::The median age of chronic myeloid leukemia (CML) patients is ~60 years, and age is still considered an important prognostic factor, included in Sokal and EURO risk scores. However, few data are available about the long-term outcome of older patients treated with imatinib (IM) frontline. We analyzed the relationship be...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-12-324228
更新日期:2011-05-26 00:00:00
abstract::The VLA-4 integrin (CD49d/CD29), initially discovered on lymphoid cells, is actually known to be highly expressed on T cells, B cells, monocytes, and derived cell lines. Unlike other VLA integrins, mainly involved in cell-matrix adhesive interactions, VLA-4 has also been implicated in several cellular interactions. Ba...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Fetal hemoglobin (HbF) and adult hemoglobin (HbA) synthesis was studied in fetal baboons, Papio cynocephalus, to determine the normal pattern of hemoglobin production during fetal development. Fetuses ranging from 53 to 180 days gestation (term gestation 184 days) were used. Erythroid cells were incubated with 3H-L-le...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are members of the interleukin-6 (IL-6) subfamily of cytokines that use a common signal transducer gp130. Human OSM (hOSM) and LIF share a functional high-affinity receptor that is composed of gp130 and LIF receptor beta subunit (LIFRbeta). A second high-affinity...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::The mutant tg/tg mice, which do not express mi transcription factor (MITF), lack mast cells in most tissues. Since MITF is expressed in both mast cells and tissues where mast cells develop, there is a possibility that the tg/tg mice may show abnormalities in both mast cell precursors and tissue environments. We examin...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-01-0247
更新日期:2004-09-15 00:00:00
abstract::The von Willebrand factor propeptide, vW AgII, has been shown to be required for the formation of vWF multimers and sorting of vWF to storage granules; whether these 2 processes are independent events has been unclear. Chimeric constructs of human and canine vWF were developed to further define these processes and to ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::Recent data suggest that CD8+ T-cell effector activity is an important component in the control of HIV replication in elite controllers (ECs). One critical element of CD8+ T-cell effector function and differentiation is the T-box transcription factor T-bet. In the present study, we assessed T-bet expression, together ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-12-322727
更新日期:2011-04-07 00:00:00
abstract::Sickle cell disease (SCD) is characterized by recurring episodes of vascular occlusion in which neutrophil activation plays a major role. The disease is associated with chronic hemolysis with elevated cell-free hemoglobin and heme. The ensuing depletion of heme scavenger proteins leads to nonspecific heme uptake and h...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-10-529982
更新日期:2014-06-12 00:00:00
abstract::Adaptor protein-3 (AP-3) is an ubiquitous cytoplasmic complex that shuttles cargo proteins from the trans-Golgi and a tubular-endosomal compartment to endosome-lysosome-related organelles. Lack of the beta3A subunit of this complex causes Hermansky-Pudlak syndrome type 2, an autosomal recessive disease characterized b...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-11-4398
更新日期:2006-06-15 00:00:00
abstract::To identify molecularly defined subgroups in multiple myeloma, gene expression profiling was performed on purified CD138(+) plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/GMMG-HD4 trial. Hierarchical clustering identified 10 subgroups; 6 corresponded to clusters desc...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-12-261032
更新日期:2010-10-07 00:00:00
abstract::The primate erythrocyte (E) complement receptor, CR1, is a transmembrane glycoprotein located in clusters on the surface of E. In vivo studies have demonstrated that during processing and clearance of complement-opsonized immune complexes, large amounts of immunoglobulin G (IgG) can be bound to primate E via CR1 with ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::Because of continuous blood transfusions, thalassemia patients are subjected to peroxidative tissue injury by the secondary iron overload. In accordance, analysis of serum from 42 beta-thalassemia patients, aged 4 to 40 years, showed that the mean concentrations of conjugated diene lipid hydroperoxides (CD), lipoperox...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::To prospectively evaluate allogeneic stem cell transplantation (allo-SCT) for myeloma as part of first-line therapy, a donor versus no-donor analysis was performed of patients treated in the HOVON-50 study, a study that was originally designed to examine thalidomide combined with intensive therapy. Two hundred sixty p...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2011-11-393801
更新日期:2012-06-28 00:00:00
abstract::To evaluate the importance of the thymus for the reconstitution of immunity in recipients of a T-cell-depleted bone marrow, we measured the appearance of CD4(+)CD45RA(+)RO(-) naive T cells (thymic rebound), restoration of the diversity of the T-cell-receptor (TCR) repertoire and the response to vaccinations with tetan...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-09-15 00:00:00
abstract::We genotyped 370 subjects with primary myelofibrosis (PMF) and 148 with postpolycythemia vera/postessential thrombocythemia (PPV/PET) MF for mutations of EZH2. Mutational status at diagnosis was correlated with hematologic parameters, clinical manifestations, and outcome. A total of 25 different EZH2 mutations were de...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-06-363424
更新日期:2011-11-10 00:00:00
abstract::To clarify the nature of null cell acute lymphoblastic leukemia (ALL) we tested null lymphoblasts and other leukemic cells for human T and B lymphocyte antigens detected by reciprocally absorbed rabbit antisera prepared against autologous T and B lymphoblast cell lines HSB-2 and SB. Blasts from 4 of 4 patients with T ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract::The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potential opportunity for treatment of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly comm...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020005037
更新日期:2020-11-19 00:00:00
abstract::A recent clinical trial for adrenoleukodystrophy (ALD) showed the efficacy and safety of lentiviral vector (LV) gene transfer in hematopoietic stem progenitor cells. However, several common insertion sites (CIS) were found in patients' cells, suggesting that LV integrations conferred a selective advantage. We performe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-09-306761
更新日期:2011-05-19 00:00:00
abstract::Age-associated clonal hematopoiesis caused by acquired mutations in myeloid cancer-associated genes is highly prevalent in the normal population. Its etiology, biological impact on hematopoiesis, and oncogenic risk is poorly defined at this time. To gain insight into this phenomenon, we analyzed a cohort of 2530 relat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-04-777029
更新日期:2017-08-10 00:00:00
abstract::Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cy...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2007-07-101139
更新日期:2008-01-15 00:00:00
abstract::The mechanisms by which hematopoietic progenitor cells become lineage-committed remain poorly understood. A cloned subline of the AML14 cell line (AML14.3D10) that spontaneously differentiates to eosinophilic myelocytes in the absence of cytokine stimulation was obtained by limiting dilution. This subline exhibits aug...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-11-15 00:00:00
abstract::NOTCH1 is mutated in 10% of chronic lymphocytic leukemia (CLL) patients and is associated with poor outcome. However, NOTCH1 activation is identified in approximately one-half of CLL cases even in the absence of NOTCH1 mutations. Hence, there appear to be additional factors responsible for the impairment of NOTCH1 deg...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2018-09-874529
更新日期:2019-02-21 00:00:00
abstract::Mast cells may be cultured from human peripheral blood in the presence of recombinant human stem cell factor (rhSCF). The characteristics of the cells in peripheral blood that give rise to mast cells are unknown. Because mast cell precursors in human marrow are CD34+, human peripheral blood mononuclear cells from pati...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-10-15 00:00:00
abstract::Acute promyelocytic leukemia (APL) has a specific genetic rearrangement between the retinoic acid receptor (RAR)-alpha gene and the pml nuclear protein gene. All-trans retinoic acid (ATRA) induces granulocytic differentiation of APL-derived cells and is used to treat APL patients. However, ATRA interacts with normal c...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-06-15 00:00:00
abstract::The HOXA9 homeoprotein exerts dramatic effects in hematopoiesis. Enforced expression of HOXA9 enhances proliferation of primitive blood cells, expands hematopoietic stem cells (HSCs), and leads to myeloid leukemia. Conversely, loss of HOXA9 inhibits proliferation and impairs HSC function. The pathways by which HOXA9 a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-08-043356
更新日期:2007-06-01 00:00:00
abstract::Human recombinant interleukin-4 (IL-4) was studied for its effects on myeloid progenitor cells from normal and leukemic bone marrow cells in the presence and absence of additional growth factors. IL-4 itself did not support myeloid cluster or colony formation (CFU-GM). However, cultures supplied with IL-4 (300 U/mL) a...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::We prepared a heterohybrid cell line that secretes a human IgM monoclonal autoantibody that recognizes an antigen found on thrombin-activated or stored platelets. The surface expression of the epitope recognized by this autoantibody, 5E5, increases with time as platelets age in vitro, suggesting that it may represent ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::Activating mutations of the Fms-like tyrosine kinase 3 (FLT3) receptor are the most common genetic alteration in acute myeloid leukemia (AML). Two distinct groups of FLT3 mutations are found: internal tandem duplications (ITDs) of the juxtamembrane region and point mutations within the tyrosine kinase domain (TKD). Re...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-11-4430
更新日期:2005-06-15 00:00:00