Abstract:
:The human interleukin-3 receptor (IL-3R) is expressed on myeloid, lymphoid, and vascular endothelial cells, where it transduces IL-3-dependent signals leading to cell activation. Although IL-3R activation may play a role in hematopoiesis and immunity, its aberrant expression or excessive stimulation may contribute to pathologic conditions such as leukemia, lymphoma, and allergic reactions. We describe here the generation and characterization of a monoclonal antibody (MoAb), 7G3, which specifically binds to the IL-3R alpha-chain and completely abolishes its function. MoAb 7G3 immunoprecipitated and recognized in Western blots the IL-3R alpha-chain expressed by transfected cells and bound to primary cells expressing IL-3R alpha. MoAb 7G3 bound the IL-3R alpha-chain with a kd of 900 pmol/L and inhibited 125I-IL-3 binding to high- and low-affinity receptors in a dose-dependent manner. Conversely, IL-3 but not granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited 125I-7G3 binding to high- and low-affinity IL-3Rs, indicating that MoAb 7G3 and IL-3 bind to common or adjacent sites. In keeping with the inhibition of IL-3 binding, MoAb 7G3 antagonized IL-3 biologic activities, namely stimulation of TF-1 cell proliferation, basophil histamine release, and IL-6 and IL-8 secretion from human endothelial cells. Two other anti-IL-3R alpha-chain MoAbs failed to inhibit IL-3 binding or function. Epitope mapping experiments using truncated IL-3R alpha-chain mutants and IL-3R alpha/GM-CSFR alpha chimeras revealed that 31 amino acids in the N-terminus of IL-3R alpha were required for MoAb 7G3 binding. MoAb 7G3 may be of clinical significance for antagonizing IL-3 in pathologic conditions such as some myeloid leukemias, follicular B-cell lymphoma, and allergy. Furthermore, these results implicate the N-terminal domain of IL-3R alpha in IL-3 binding. Since this domain is unique to the IL-3/GM-CSF/IL-5 receptor subfamily, it may represent a novel and common binding feature in these receptors.
journal_name
Bloodjournal_title
Bloodauthors
Sun Q,Woodcock JM,Rapoport A,Stomski FC,Korpelainen EI,Bagley CJ,Goodall GJ,Smith WB,Gamble JR,Vadas MA,Lopez AFsubject
Has Abstractpub_date
1996-01-01 00:00:00pages
83-92issue
1eissn
0006-4971issn
1528-0020journal_volume
87pub_type
杂志文章相关文献
BLOOD文献大全abstract::Platelet factor 4 (PF4) is an abundant platelet alpha-granule C-X-C chemokine that has weak chemotactic potency but strongly inhibits hematopoiesis through an unknown mechanism. We find that PF4 binds to human CD34+ hematopoietic progenitor cells (HPCs) with a median effective concentration of 1 microg/mL but not afte...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-08-2363
更新日期:2003-06-15 00:00:00
abstract::Mice deficient in intercellular adhesion molecule-1 (ICAM-1), lacking membranous ICAM-1, show a normal development but abnormalities of inflammatory and immune functions. Although the membrane-bound form of ICAM-1 is not detectable in the mutant strain, circulating ICAM-1 (cICAM) is present in serum from ICAM-1-defici...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-02-15 00:00:00
abstract::The turnover rates of beta and gamma globin messenger RNAs and of beta and gamma globin protein synthesis in human reticulocytes have been measured. Our goal was to determine whether beta globin mRNA is significantly more stable than gamma globin mRNA during the final stages of erythroid cell maturation. Such a result...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-11-01 00:00:00
abstract::Reduced levels of somatic hypermutation (SHM) have recently been described in IgG-switched immunoglobulin genes in a minority of patients with common variable immunodeficiency (CVID), demonstrating a disruption of the normal linkage between isotype switch and SHM. To see if, irrespective of isotype, there is a tendenc...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-12-4359
更新日期:2005-01-15 00:00:00
abstract::Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-08-01 00:00:00
abstract::On encountering a danger signal, dendritic cells (DCs) undergo a complex maturation process and become specialized in antigen presentation. We previously reported that engagement of major histocompatibility complex (MHC) class II molecules located on immature DCs in membrane rafts by lymphocyte activation gene-3 (LAG-...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-01-0273
更新日期:2003-09-15 00:00:00
abstract::It has been shown that histamine induces early changes on endothelial cells (EC), such as a transient expression of P-selectin and secretion and/or surface expression of early mediators (eg, prostacyclin [PG1(2)], platelet-activating factor [PAF], and leukotriene B4 [LTB4]). However, delayed effects of histamine on EC...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::Drug-dependent antibodies (DDAbs) that cause acute thrombocytopenia upon drug exposure are nonreactive in the absence of the drug but bind tightly to a platelet membrane glycoprotein, usually α(IIb)/β3 integrin (GPIIb/IIIa) when the drug is present. How a drug promotes binding of antibody to its target is unknown and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-04-643148
更新日期:2015-10-29 00:00:00
abstract::Donor hematopoietic stem cells (HSCs) can correct T-cell deficiencies in patients with severe combined immunodeficiency by replacing resident thymus cells. However, as those progenitors that naturally migrate to the thymus are not capable of supporting long-term thymopoiesis, a successful transplant is thought to requ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-08-447417
更新日期:2013-03-14 00:00:00
abstract::Using age-fractionated erythrocytes, warm autoantibodies can be classified into two distinct categories, depending on their reactivity with reticulocyte-enriched (younger) or reticulocyte-poor (older) red cell fractions. The strength of the direct antiglobulin test (DAT) on the age-fractionated red cells of 24 patient...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Human mast cells in adult tissues have been thought to have limited, if any, proliferative potential. The current study examined mast cells obtained from adult skin and cultured in serum-free medium with recombinant human stem cell factor. During the first 4 weeks of culture, the percentages of mast cells increased fr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.7.2045
更新日期:2001-04-01 00:00:00
abstract::The International Prognostic Scoring System (IPSS) has been widely used to predict the prognosis of patients with myelodysplastic syndrome (MDS). However, IPSS does not always provide a sufficiently precise evaluation of patients to allow the appropriate choice of clinical interventions. Here, we analyzed the expressi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-06-2393
更新日期:2006-01-01 00:00:00
abstract::During an 8-year period, 28 young adults (median age 27 years) and 30 children (median age 10 years) with severe aplastic anemia have received allogeneic bone marrow transplantation (BMT) from major histocompatibility locimatched sibling donors after preparation with cyclophosphamide and total lymphoid irradiation (TL...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::Peripheral lymphocytes from normal individuals and from patients with chronic lymphocytic leukemia (CLL) were cultured in vitro for 1-7 days. The growth response to phytohemagglutinin (PHA) was quantitated by the incorporation of tritiated uridine into RNA nucleotide during a 2-hr pulse with the radioisotope. While th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::Hemophilia B Leyden is an X chromosome-linked bleeding disorder characterized by an altered developmental expression of blood coagulation factor IX. This form of hemophilia B has been found to be associated with a variety of single point mutations in the factor IX promoter region. We now describe a novel point mutatio...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-07-01 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::Autosomal recessive STAT1 deficiency is associated with impaired cellular responses to interferons and susceptibility to intracellular bacterial and viral infections. We report here a new form of partial STAT1 deficiency in 2 siblings presenting mycobacterial and viral diseases. Both carried a homozygous missense muta...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-04-280586
更新日期:2010-12-23 00:00:00
abstract::Gene therapy holds a major promise. However, until now, this promise was fulfilled only in few cases, in rare genetic diseases. One very common clinical condition is anemia. Patients with anemia of chronic renal failure are treated with erythropoietin. The objective of this study was to develop a therapeutic platform ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-11-4174
更新日期:2005-10-01 00:00:00
abstract::Chemokines as well as the signaling through the adhesion molecules intercellular adhesion molecule (ICAM)-3 and CD43 are able to induce in T lymphocytes their switching from a spherical to a polarized motile morphology, with the formation of a uropod at the rear of the cell. We investigated here the role of CD43 in th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-06-15 00:00:00
abstract::A Y-chromosome-specific in situ hybridization assay was used to assess the frequency with which host bone marrow cells are retained after marrow grafting. The majority of patients (74%) showed the presence of both host and donor marrow cells when assayed 14 days after transplant. By 84 days posttransplant only 4% of t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::ADAMTS13 proteolytically regulates the platelet-tethering function of von Willebrand factor (VWF). ADAMTS13 function is dependent upon multiple exosites that specifically bind the unraveled VWF A2 domain and enable proteolysis. We carried out a comprehensive functional analysis of the ADAMTS13 cysteine-rich (Cys-rich)...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-08-594556
更新日期:2015-03-19 00:00:00
abstract::Acute promyelocytic leukemia (APL) is typified by the t(15;17) translocation, which leads to the formation of the PML/RARA fusion gene and predicts a beneficial response to retinoids. However, approximately 10% of all APL cases lack the classic t(15;17). This group includes (1) cases with cryptic PML/RARA gene rearran...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::Immunizing bone marrow donors prior to bone marrow transplant (BMT) has the potential for adoptively transferring specific immunity against opportunistic pathogens. Studies have shown that long-term antibody production occurs in the bone marrow and that specific humoral immunity may be transferred from donor to recipi...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::Heparin-induced thrombocytopenia (HIT) with thrombosis is a serious complication of heparin use. HIT sera can generate platelet-derived microparticles, which are produced in a heparin-dependent manner and are hypothesized to be important initial pathological participants because they promote vascular occlusion. To dat...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract::We have identified an intergenic transcriptional activity that is located between the human HOXA1 and HOXA2 genes, shows myeloid-specific expression, and is up-regulated during granulocytic differentiation. The novel gene, termed HOTAIRM1 (HOX antisense intergenic RNA myeloid 1), is transcribed antisense to the HOXA g...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-06-162164
更新日期:2009-03-12 00:00:00
abstract::Optimal conditions necessary for the cytochemical demonstration of megakaryocyte (Mk) and platelet acid phosphatase (AP) were determined. Methanol, a constituent of fixatives commonly used in AP cytochemistry, was found to inhibit MkAP, and the degree of inhibition varied with Mk maturity. Immature Mk contained predom...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-11-01 00:00:00
abstract::A1, a bcl-2 family member, has been identified as a hematopoietic-specific, early inducible gene. In this study it is shown that stable transfection of A1 into an interleukin-3 (IL-3)-dependent myeloid precursor cell line, 32D c13, leads to a retardation of IL-3 withdrawal-induced cell death similar to that observed w...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Small nuclear U1-RNAs (snRNAs), the spliceosome components selectively recognizing donor splice sites (5'ss), were engineered to restore correct mRNA processing in a cellular model of severe coagulation factor VII (FVII) deficiency, caused by the IVS7 9726 + 5g/a change. Three U1-snRNAs, complementary to the mutated 5...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-10-117440
更新日期:2008-03-01 00:00:00
abstract::We confirmed that murine hematopoietic stem cells express the c-kit molecule but not lymphohematopoietic lineage markers. These lineage marker-negative c-kit-positive (Lin- c-kit+) cells were further divided according to the uptake of rhodamine-123 (Rh-123). Approximately 1,000 Lin- c-kit+ rhodamine-123dull cells, whi...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::In vitro agar culture patterns of bone marrow cells in acute myeloid leukemia may show several growth patterns, including cultures where no colonies or clusters develop, cultures with varying numbers of clusters and no colonies, or colony and cluster formation with an extremely high ratio of clusters to colonies. Twel...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1979-08-01 00:00:00