Abstract:
:The phagocyte nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase was functionally reconstituted in monkey kidney COS-7 cells by transfection of essential subunits, gp91(phox), p22(phox), p47(phox), and p67(phox). COS-7 cells express the essential small guanosine 5'-triphosphatase, Rac1. Transgenic COS-phox cells were capable of arachidonic acid-induced NADPH oxidase activity up to 80% of that of human neutrophils, and of phorbol myristate acetate (PMA)-induced activity up to 20% of that of neutrophils. Expression of all 4 phox components was required for enzyme activity, and enzyme activation was associated with membrane translocation of p47(phox), p67(phox), and Rac1. Expression of p47(phox) Ser303Ala/Ser304Ala or Ser379Ala phosphorylation-deficient mutants resulted in significantly impaired NAPDH oxidase activity, compared with expression of wild-type p47(phox) or the p47(phox) Ser303Glu/Ser304Glu phosphorylation mimic, suggesting that p47(phox) phosphorylation contributes to enzyme activity in the COS system, as is the case in neutrophils. Hence, COS-phox cells should be useful as a new whole-cell model that is both capable of high-level superoxide production and readily amenable to genetic manipulation for investigation of NADPH oxidase function. PMA-elicited superoxide production in COS-phox cells was regulated by activation of protein kinase C (PKC) and Rac. Although COS-7 cells differ from human neutrophils in PKC isoform expression, transient expression of major neutrophil isoforms in COS-phox cells did not increase PMA-induced superoxide production, suggesting that endogenous isoforms were not rate limiting. Val204 in p67(phox), previously shown to be required for NADPH oxidase activity under cell-free conditions, was found to be essential for superoxide production by intact COS-phox cells, on the basis of transfection studies using a p67(phox) (Val204Ala) mutant.
journal_name
Bloodjournal_title
Bloodauthors
Price MO,McPhail LC,Lambeth JD,Han CH,Knaus UG,Dinauer MCdoi
10.1182/blood.v99.8.2653subject
Has Abstractpub_date
2002-04-15 00:00:00pages
2653-61issue
8eissn
0006-4971issn
1528-0020journal_volume
99pub_type
杂志文章相关文献
BLOOD文献大全abstract::The developmental relationship between the blood and endothelial cell (EC) lineages remains unclear. In the extra-embryonic blood islands of birds and mammals, ECs and blood cells are closely intermixed, and blood island precursor cells in the primitive streak express many of the same molecular markers, leading to the...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-03-490045
更新日期:2013-12-05 00:00:00
abstract::Using recombinantly expressed proteins and synthetic peptides, we examined the structural/functional features of the platelet chemokines, neutrophil-activating peptide-2 (NAP-2) and platelet factor 4 (PF4); that were important in their activation of neutrophils. Previous studies with the chemokine interleukin-8 (IL-8)...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::The treatment of multiple myeloma has evolved significantly over the last decades from primarily alkylator-based chemotherapeutic agents with minimal efficacy to the introduction of more effective agents including immune modulators and proteasome inhibitors, which have changed the landscape of therapy for this disease...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-05-636357
更新日期:2016-09-29 00:00:00
abstract::We report on a second generation of transgenic mice produced by crossing a transgenic mouse line expressing high levels of human alpha and beta S chains (alpha H beta S [beta MDD]) with a line expressing human alpha and beta S-Antilles (beta SAnt). We hypothesized that mice expressing both hemoglobins (Hbs) would have...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-09-15 00:00:00
abstract::The role of T-cell subsets in the induction of tissue factor (TF) production by human monocytes in vitro was investigated. Mitogen stimulation enabled both unfractionated T cells and their CD4+ or CD8+ subsets to promote procoagulant activity (PCA). After mitogen or antigen activation, all seven T-cell clones with Th1...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract::Follicular lymphoma (FL) is characterized by a relatively indolent clinical course, but the disease often transforms into a more aggressive large cell lymphoma with a rapidly progressive clinical course. In the present study, we analyzed 41 cases of FL known to have subsequently transformed to aggressive lymphoma and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-08-2482
更新日期:2003-08-15 00:00:00
abstract::The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is chronic intravascular hemolysis that is a consequence of unregulated activation of the alternative pathway of complement (APC). Intravascular hemolysis can be inhibited in patients by treatment with eculizumab, a monoclonal antibody that binds compl...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-09-244285
更新日期:2010-03-18 00:00:00
abstract::Immune deficiency viruses such as SIV in macaques or HIV-1 in human beings have evolved mechanisms to defeat host immunity that also impact the efficacy of vaccines. A key factor for vaccine protection is whether immune responses elicited by prior immunization remain at levels sufficient to limit disease progression o...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-202655
更新日期:2009-08-06 00:00:00
abstract::Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in physiologic and pathologic angiogenesis. Plasma membrane (PM) levels of VEGFR2 are regulated by endocytosis and secretory transport through the Golgi apparatus. To date, the mechanism whereby the VEGFR2 traffics through the Golgi apparatus rema...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-06-291690
更新日期:2011-01-27 00:00:00
abstract::The expansion of follicular lymphomas (FLs) resembles, both morphologically and functionally, normal germinal center B-cell growth. The tumor cells proliferate in networks of follicular dendritic cells and are believed to be capable of somatic hypermutation and isotype switching. To investigate the relation between so...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract::The iron absorption from ferritin and hemosiderin biosynthetically labeled with radioiron was studied in 108 subjects. The geometric mean absorption of ferritin iron in both normal and iron-deficient subjects was 1.9 percent. Its mean absorption ranged from 0.9 percent in normal subjects to 2.5 percent in subjects wit...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1975-05-01 00:00:00
abstract::Chronic lymphocytic leukemia is characterized by relapse after treatment and chemotherapy resistance. Similarly, in other malignancies leukemia cells accumulate mutations during growth, forming heterogeneous cell populations that are subject to Darwinian selection and may respond differentially to treatment. There is ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-05-433540
更新日期:2012-11-15 00:00:00
abstract::The Hermes receptor CD44 is a multifunctional adhesion molecule that plays an essential role in the homing and invasion of neoplastic stem cells in various myeloid malignancies. Although mast cells (MCs) reportedly express CD44, little is known about the regulation and function of this receptor in neoplastic cells in ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2018-02-833582
更新日期:2018-11-01 00:00:00
abstract::ELL-12, a liposome formulation of the ether-lipid 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH(3)), is a nonmyelosuppressive antiproliferative agent that is more effective and less toxic than the ether lipid itself in tumor model systems. We found that ELL-12 induced apoptosis in Jurkat, H9, and U-9...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-11-15 00:00:00
abstract::Ras-related C3 botulinum toxin substrate 2 (RAC2), through interactions with reduced NAD phosphate oxidase component p67 phox , activates neutrophil superoxide production, whereas interactions with p21-activated kinase are necessary for fMLF-induced actin remodeling. We id...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2018-11-886028
更新日期:2019-05-02 00:00:00
abstract::We demonstrated that Flk-1(+) cells derived from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) to suffice as vascular progenitor cells (VPCs). In the present study, we investigated the importance of the stage of ES cell differentiation on effective participat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-06-1877
更新日期:2003-04-01 00:00:00
abstract::The MLLT10 gene, located at 10p13, is a known partner of MLL and PICALM in specific leukemic fusions generated from recurrent 11q23 and 11q14 chromosome translocations. Deep sequencing recently identified NAP1L1/12q21 as another MLLT10 partner in T-cell acute lymphoblastic leukemia (T-ALL). In pediatric T-ALL, we have...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-02-487256
更新日期:2013-06-20 00:00:00
abstract::The exact mechanisms underlying the role of oxidative stress in the pathogenesis and the prothrombotic or proinflammatory status of antiphospholipid syndrome (APS) remain unknown. Here, we investigate the role of oxidative stress and mitochondrial dysfunction in the proatherothrombotic status of APS patients induced b...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-12-400986
更新日期:2012-06-14 00:00:00
abstract::Derivative chromosome 9 deletions are seen in 10% to 15% of patients with chronic myelogenous leukemia and have been associated with a poor prognosis; however, no studies have been performed in the context of a randomized clinical trial. We developed a DNA-based deletion screen and investigated 339 chronic phase patie...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-02-074252
更新日期:2007-08-15 00:00:00
abstract::Sequential immunologic, cytochemical, and cytokinetic studies were done on single lymphoid cells in the peripheral blood of 6 children with infectious mononucleosis (IM) and 1 child with toxoplasmosis 1-2 wk after onset of symptomatology. The absolute number of AET-SRBC rosetting (E+) cells was increased in all patien...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00
abstract::The Smad-signaling pathway downstream of the transforming growth factor-beta superfamily of ligands is an evolutionarily conserved signaling circuitry with critical functions in a wide variety of biologic processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have b...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-02-005611
更新日期:2006-12-15 00:00:00
abstract::We examined the role of the T-cell antigen CD2 in the regulation of erythropoiesis by the lymphokine cascade. T-cell interleukin-2 (IL-2) receptors (p55) were induced via triggering of the antigen receptor-associated CD3 epitope. Before CD3 triggering T cells were preincubated with a CD2-blocking (Leu-5b) or isotype c...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::The combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and 2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leuke...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2006-03-011908
更新日期:2007-02-15 00:00:00
abstract::Human bone marrow (BM) cells contain low levels of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, which may explain their susceptibility to nitrosourea-induced cytotoxicity and the development of secondary leukemia after nitrosourea treatment. Isolated CD34+ myeloid progenitors were also found to have l...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 (FLT3) gene occurs in 30% of acute myeloid leukemias (AMLs) and confers a poor prognosis. Thirteen relapsed or chemo-refractory FLT3-ITD(+) AML patients were treated with sorafenib (200-400 mg twice daily). Twelve patients showed clearance or near ...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2011-06-363960
更新日期:2012-05-31 00:00:00
abstract::Tumor necrosis factor (TNF) and lymphotoxin (LT; TNF-beta) are major cytokines produced by B lymphocytes. Stimulation by okadaic acid, a phosphatase 1 and 2A inhibitor, markedly increased TNF mRNA accumulation and cytokine production. On the other hand, the accumulation of LT mRNA was not affected by okadaic acid desp...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::Commercial porcine factor VIII concentrate (Hyate:C) is effective in treatment of patients with hemophilia A who have circulating antibodies to factor VIII. The molecular forms of factor VIII in the concentrate were identified and evaluated in light of the known properties of porcine and human factor VIII. The factor ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Twenty consecutive patients with Hodgkin disease in continuous complete remission and off treatment for at least 5 yr (range 5-25 yr, median 9 yr) were studied with a battery of immunologic parameters. Skin test reactivity to four common antigens, sensitization to 2,4-dinitrochlorobenzene, absolute lymphocyte count, r...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract::Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an internatio...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019003453
更新日期:2020-05-21 00:00:00
abstract::There is evidence from bone marrow transplantation that T cells may be involved in the immunologic control of leukemia. But many patients relapse despite a potent graft-versus-leukemia effect mediated by allogeneic T cells. The expression of the FasL protein has been suggested as a mechanism of tumor immune escape. We...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00