Abstract:
:The human pluripotent UT-7 cell line is growth factor-dependent for proliferation and differentiation. We have previously shown that (1) granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo) induce a myeloid and erythroid pattern of differentiation, respectively; (2) GM-CSF acts predominantly over Epo for cell differentiation; (3) GM-CSF induces a rapid downmodulation (4 hours) of Epo receptors (Epo-R) at the mRNA and binding site levels; and (4) in contrast, Epo has no effect on GM-CSF receptor (GM-CSF-R) expression. These results suggested that UT-7 cell commitment or differentiation may be directed by a hierarchical action of growth factors through an early and rapid transmodulation of growth factor receptors. To test this hypothesis, we introduced and expressed the murine Epo-R (muEpo-R) in UT-7 cells using a retroviral strategy. Two retroviral vectors were constructed: one carrying the neomycin resistance gene, and another carrying a mouse Epo-R cDNA devoid of its regulatory untranslated 3' sequence placed under the transcriptional control of the viral long terminal repeat element (LTR) and the neomycin resistance gene. Three UT-7/Epo-R infected clones (12, 6, 10) and one UT-7/neomycin clone (Neo) were selected in medium containing G418. After growth factor deprivation (18 hours), Epo-Rs were expressed at the same level (approximately 6,000 receptors per cell) in all four clones 12, 6, 10, Neo, and in parental UT-7 cells, and exhibited similar affinity (0.1 to 0.2 nmol/L). Cross-linking experiments showed that Epo is associated with three proteins of about 66, 85, and 100 kD in cells of parental UT-7, as well as in cells of clones 10 and 12. An inhibitory antibody directed specifically against the human Epo-R (huEpo-R Ab) abolished almost completely the cross-linking on parental UT-7 cells, but not on cells of clone 12, demonstrating that more than 90% cell surface Epo-Rs were of murine origin. The presence of GM-CSF significantly reduced the number of Epo-Rs expressed on parental UT-7 cells, but not on cells of clones 12, 10, and 6. HuEpo-R Ab inhibited Epo-induced parental UT-7 cell growth, but not that of cells of clone 12, suggesting that the muEpo-R is able to induce human UT-7 cell proliferation. When cells of clone 12 were switched from a medium containing GM-CSF to one with Epo, cell surface glycophorin A (GPA) was induced, as in parental UT-7 cells without inhibition by the huEpo-R Ab, demonstrating that the muEpo-R is also able to transduce a differentiation signal in human cells. However, in cells of clones 12, 6, 10 and Neo, as well as in parental UT-7 cells, the induction of GPA by Epo was inhibited by GM-CSF. This finding demonstrates that, although GM-CSF does not downregulate muEpo-R binding sites on UT-7/muEpo-R infected clones, it still inhibits the effects of Epo on cell differentation. Therefore, hierarchical regulation induced by growth factors for cell commitment or differntiation more likely acts downstream of cell surface receptors at either the signal transduction or transcriptional levels.
journal_name
Bloodjournal_title
Bloodauthors
Hermine O,Dubart A,Porteux F,Mayeux P,Titeux M,Dumenil D,Vainchenker Wsubject
Has Abstractpub_date
1996-03-01 00:00:00pages
1746-53issue
5eissn
0006-4971issn
1528-0020journal_volume
87pub_type
杂志文章相关文献
BLOOD文献大全abstract::Marginal zone B-cell lymphoma (MZL) is a recently individualized lymphoma that encompasses mucosa-associated lymphoid tissue (MALT) lymphoma, splenic lymphoma with or without villous lymphocytes, and nodal lymphoma with or without monocytoid B-cells. If the clinical description and outcome of MALT lymphoma is well kno...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-03-15 00:00:00
abstract::K-562 human leukemia cells grown in the presence of specific goat anti-K-562 gamma globulin, F(ab)'2, Fab', or Fab showed a decrease in DNA and protein syntheses and a loss of cell viability within several hours. Eventually all cells died and lysed within 2-5 days. These events occurred in the absence of added effecto...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::Activated ras genes are often associated with human myeloid leukemias with a monocytic differentiated phenotype. To investigate the role of the activated ras gene in leukemogenesis, a myeloid nontumorigenic cell line (FDC-P1) was infected with a selectable retroviral vector carrying the v-Ha-ras gene (H1neo). Infected...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::The Gardos channel is a Ca(2+)-sensitive, intermediate conductance, potassium selective channel expressed in several tissues including erythrocytes and pancreas. In normal erythrocytes, it is involved in cell volume modification. Here, we report the identification of a dominantly inherited mutation in the Gardos chann...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-04-642496
更新日期:2015-09-10 00:00:00
abstract::Two distinct classes of granulocyte progenitor cells present in normal mouse bone marrow are expressed sequentially in the vivo plasma clot diffusion chamber culture system. By several criteria, progenitor cells giving rise to granulocyte colonies on day 4 of culture (CFU-D4) are different from those giving rise to co...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-04-01 00:00:00
abstract::Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor of the extrinsic coagulation system, synthesized in endothelial cells, which has recently been shown to play an important role in the regulation of activated coagulation factors at the endothelial cell surface. In the present study we investigated t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
abstract::The majority of patients with Hodgkin lymphoma (HL) are cured with initial therapy. However, high-dose therapy with autologous hematopoietic cell transplant (AHCT) allows for the cure of an additional portion of patients with relapsed or primary refractory disease. Positron emission tomography-negative complete remiss...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2017-09-772673
更新日期:2018-04-12 00:00:00
abstract::Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associated IgG (PA-IgG) levels were also m...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-05-01 00:00:00
abstract::Interleukin 21 (IL-21) is a member of the common gamma-chain family of cytokines, which influence a broad spectrum of immunologic responses. A number of studies have examined the function of IL-21, but its specific role in Th1/Th2-cell differentiation and related effector responses remains to be clarified. Thus, we ge...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-021600
更新日期:2007-03-01 00:00:00
abstract::Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is emerging as a new regulator of immune responses and inflammatory vascular diseases. Although IL-33 and its cognate receptor ST2 appear to be expressed in vascular cells, the precise role of IL-33 in the vasculature has not been determined. In this study,...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-203372
更新日期:2009-10-01 00:00:00
abstract::The pathogenesis of acute painful crisis in children with sickle cell disease is poorly understood; suggested risk factors include sickle cell type, severity of anemia, fetal hemoglobin concentration, and hypoxemia from upper airway obstruction. In a cohort study of 95 patients the relationship between clinical, labor...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-05-1392
更新日期:2003-02-01 00:00:00
abstract::Pattern recognition receptors (PRRs) play an essential role in a macrophage's response to mycobacterial infections. However, how these receptors work in concert to promote this macrophage response remains unclear. In this study, we used bone marrow-derived macrophages isolated from mannose receptor (MR), complement re...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-024406
更新日期:2006-11-01 00:00:00
abstract::Peripheral blood mononuclear cells from five patients with essential thrombocythemia (ET) were cultured in vitro to evaluate restricted megakaryocytic (CFU-Meg), myeloid (CFU-GM), and erythroid (BFU-E) progenitor cell development. Varying concentrations of aplastic canine serum served as the source of megakaryocyte co...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
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. Transge...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.8.2653
更新日期:2002-04-15 00:00:00
abstract::We have recently demonstrated that IgD(hi) B cells can occupy an extravascular perisinusoidal niche in the bone marrow in addition to the well-established follicular niche in conventional secondary lymphoid organs. The spleen has long been considered to be the site at which newly formed B lymphocytes mature into IgD(h...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-021089
更新日期:2007-03-15 00:00:00
abstract::Ras-associated autoimmune leukoproliferative disorder (RALD) is a chronic, nonmalignant condition that presents with persistent monocytosis and is often associated with leukocytosis, lymphoproliferation, and autoimmune phenomena. RALD has clinical and laboratory features that overlap with those of juvenile myelomonocy...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2014-11-567917
更新日期:2015-04-30 00:00:00
abstract::The subcellular localization of the platelet membrane receptors glycoproteins (GP) Ib and IIb/IIIa [corrected] has been studied within resting platelets by a combination of biochemical and cytochemical techniques. While both GPIb and GPIIb/IIIa are localized within the plasma membrane and surface-connected canalicular...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-02-15 00:00:00
abstract::Primary myelofibrosis (PMF) is the most serious myeloproliferative disorder, characterized by clonal myeloproliferation associated with cytokine-mediated bone marrow stromal reaction including fibrosis and osteosclerosis. Current drug therapy remains mainly palliative. Because the NF-kappaB pathway is implicated in th...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-10-054502
更新日期:2007-07-01 00:00:00
abstract::Adult T-cell leukemia (ATL) is neoplasm of the mature helper T lymphocytes and human T-cell lymphotropic virus type-I (HTLV-I) has been shown to be causative virus of ATL. Because HTLV-I integrates its provirus randomly into host chromosomal DNA, monoclonal integration of HTLV-I provirus indicates the clonal prolifera...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::In this issue of Blood, Savona and an international consortium of clinical investigators propose uniform response criteria for treatment trials enrolling adult patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). Such a proposal is needed because new drugs are finally being tested in these rare “over...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2015-02-626473
更新日期:2015-03-19 00:00:00
abstract::Atypical hemolytic uremic syndrome (aHUS) is classically described to result from a dysregulation of the complement alternative pathway, leading to glomerular endothelial cell (EC) damage and thrombosis. However, recent findings in families with aHUS of mutations in the DGKE gene, which is not an integral component of...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-06-579953
更新日期:2015-02-05 00:00:00
abstract::P-selectin (CD62P) is a member of the selectin family of adhesion molecules involved in the regulation of leukocyte traffic. P-selectin glycoprotein ligand-1 (PSGL-1) is a mucin-like molecule that is thought to be a primary ligand for P-selectin. The interaction of P-selectin with PSGL-1 results in leukocyte rolling a...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::The status of the T cell receptor beta and gamma genes in natural killer (NK) cells was investigated in two patients with a marked expansion of CD2+, CD3- NK cells. Both genes were found to be in the germline state. The T alpha and complete T beta gene transcripts were not detected, but a 1.0-kilobase T beta gene tran...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::ASXL1 is mutated/deleted with high frequencies in multiple forms of myeloid malignancies, and its alterations are associated with poor prognosis. De novo ASXL1 mutations cause Bohring-Opitz syndrome characterized by multiple congenital malformations. We show that Asxl1 deletion in mice led to developmental abnormaliti...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-05-500272
更新日期:2014-01-23 00:00:00
abstract::Th17 cells play an essential role in the pathogenesis of autoimmune and inflammatory diseases. Most of our current understanding on Th17 cell differentiation relies on studies carried out in mice, whereas the molecular mechanisms controlling human Th17 cell differentiation are less well defined. In this study, we iden...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-01-407528
更新日期:2012-06-07 00:00:00
abstract::The PI3K/Akt/mTOR pathway has emerged as a critical regulator of dendritic cell (DC) development and function. The kinase mTOR is found in 2 distinct complexes, mTORC1 and mTORC2. In this study, we show that mTORC1 but not mTORC2 is required for epidermal Langerhans cell (LC) homeostasis. Although the initial seeding ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-06-439786
更新日期:2013-01-10 00:00:00
abstract::In utero transplantation (IUT) is becoming a viable option for the treatment of various immune and metabolic disorders diagnosed early in gestation. In this study, donor fetal liver cells had a 10-fold competitive engraftment advantage relative to adult bone marrow in allogeneic fetal severe combined immunodeficient (...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.5.1870
更新日期:2002-03-01 00:00:00
abstract::The incidence of chronic lymphocytic leukemia (CLL) in Taiwan is markedly lower than that in Western countries, but we have seen a drastically increasing trend. We explored this distinct incidence trend of CLL for Taiwanese. The epidemiologic data of CLL for Taiwanese and Caucasian Americans during 1986 to 2005 were o...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-285221
更新日期:2010-11-25 00:00:00
abstract::The effect of HbA and HbF on both the aggregation and deaggregation of deoxy HbS and deoxy HbCHarlem in concentrated phosphate buffers was studied by a turbidimetric method. Although pure deoxy HbA is fully soluble in 2.4 M potassium phosphate buffer, the same concentration of deoxy HbAS was insoluble in the same buff...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-03-01 00:00:00
abstract::Inhibition of complement-mediated granulocyte aggregation has recently been proposed as a mechanism of action of high-dose corticosteroids in shock states. Such inhibition may be effected through alteration of receptor function. Methylprednisolone inhibits binding of the synthetic chemotaxin f-methionine-leucine-pheny...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00