Abstract：
OBJECTIVE:Several transcription factors determine the cell fate decision between granulocytes and monocytes, but the upstream signal transduction pathways that govern myelopoiesis are largely unknown. Based on our observation of aberrant myeloid cell representation in hematopoietic tissues of 12/15-lipoxygenase (12/15-LOX)-deficient (Alox15) mice, we tested the hypothesis that polyunsaturated fatty acid metabolism regulates myelopoiesis. MATERIALS AND METHODS:Multicolor flow cytometric analysis and methylcellulose assays were used to compare myelopoiesis and the differentiative capacity of progenitors from Alox15 and wild-type mice. Furthermore, we elucidated the mechanism by which 12/15-LOX is involved in regulation of myelopoiesis. RESULTS:Granulopoiesis in Alox15 mice is increased while monopoiesis is reduced. Moreover, there is an accumulation of granulocyte-macrophage progenitors that exhibit defective differentiation. Mechanistically, we demonstrate that transcriptional activity of interferon regulatory factor-8 (Irf8), which regulates myelopoiesis, is impaired in Alox15 progenitors and bone marrow-derived macrophages due to loss of 12/15-LOX-mediated redox regulation of Irf8 nuclear accumulation. Restoration of redox signaling in Alox15 bone marrow cells and granulocyte-macrophage progenitors reversed the defect in myeloid differentiation. CONCLUSIONS:These data establish 12/15-LOX-mediated redox signaling as a novel regulator of myelopoiesis and Irf8.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Kinder M,Thompson JE,Wei C,Shelat SG,Blair IA,Carroll M,Puré Edoi
10.1016/j.exphem.2010.07.004subject
Has Abstractpub_date
2010-11-01 00:00:00pages
1036-1046.e1-4issue
11eissn
0301-472Xissn
1873-2399pii
S0301-472X(10)00285-7journal_volume
38pub_type
杂志文章abstract：:A fluorescence-activated cell sorter has been used to sort out enriched populations of murine hemopoietic stem cells from mouse bone marrow, based on fluorescence of cells labeled with various antisera. Significant positive enrichment for stem cells was obtained with rabbit anti-human brain, human anti-human sperm and...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-08-01 00:00:00
abstract：:Transfusion with 10,000 or 20,000 marrow cells resulted in 30+ days survival of 15%-50% of mice exposed to an Ld90 or LD100 or radiation. The use of congenic mice with alloenzyme markers permitted the identification of host and donor cells in the peripheral blood of transfused animals. Donor cells were present initial...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:The human cell line CMK spontaneously expresses megakaryocytic characteristics and can be induced to differentiate into mature megakaryocytes after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). In comparison with CMK, we have examined the characteristics of a subclone, designated as CMK11-5, that is morpholo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:The cloning efficiency of T-lymphocyte progenitor cells (CFU-T) is dependent on mononuclear cell concentration, with a triphasic growth curve. At low plating cell concentrations, hydrocortisone causes a dose-dependent decrease in cloning efficiency, whereas at high cell concentrations hydrocortisone causes increased c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:Chronic myeloid leukemia (CML) is caused by Bcr-Abl, a constitutively active tyrosine kinase that is the result of a reciprocal translocation between chromosomes 9 and 22 and cytogenetically evident as the Philadelphia chromosome. Imatinib (Glivec, Gleevec), a specific small molecule inhibitor of Bcr-Abl, has become t...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2007.01.023
更新日期：2007-04-01 00:00:00
abstract：:Assessment of donor chimerism is becoming increasingly important in patients undergoing reduced-intensity conditioning (RIC) allogeneic bone marrow transplants, due to the possibility of mixed chimeras. This regimen has been used successfully for patients with leukemia and genetic disorders with donor chimerism occurr...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.05.028
更新日期：2004-09-01 00:00:00
abstract：OBJECTIVE:We have previously reported immunity to donor antigens following in utero transplantation (IUT) of cytokine-stimulated allogeneic hematopoietic stem cells (sca(+)/lin(-)) (day 9 of gestation). Transplanted mice showed accelerated rejection of donor skin grafts and high anti-donor cytotoxic response, a finding...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00803-2
更新日期：2002-06-01 00:00:00
abstract：:Ouabain has been shown to increase the number of clonally derived erythroid stem cells, CFUE and BFUE, from normal murine bone marrow. We report here that digoxin and theophylline also enhance erythroid stem cell colony formation, in the presence of suboptimal concentrations of erythropoietin (Ep) (0.01 IU/ml) in meth...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
abstract：OBJECTIVE:Morbidity and mortality occurring in patients with multiple myeloma, AL amyloidosis, and light chain deposition disease can result from the pathologic deposition of monoclonal immunoglobulin light chains (LCs) in kidneys and other organs. To reduce synthesis of such components, therapy for these disorders typ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.07.001
更新日期：2010-11-01 00:00:00
abstract：:Washed canine platelets were shown to express a significant level of von Willebrand factor (vWf). Canine platelet vWf differed from canine plasma vWf by the absence of satellite bands associated with each multimer when resolved by SDS-agarose gel electrophoresis. Expression and multimeric composition of canine platele...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:A transplanted tumor that induces granulocytosis and produces colony stimulating factor (CSF) was studied in mice during several passages. The sequence of events leading to granulocytosis was characterized. Band granulocytes were increased 3 days after tumor inoculation, while simultaneously CFU-s and CFU-c in bone ma...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-04-01 00:00:00
abstract：:Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00112-5
更新日期：1999-12-01 00:00:00
abstract：OBJECTIVE:The significant role of direct contact between hematopoietic progenitor cells (HPC) and the cellular microenvironment for maintaining "stemness" has been demonstrated. Human mesenchymal stem cell (MSC) feeder layers represent a surrogate model for this interaction. Specific adhesion molecules are responsible ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.10.003
更新日期：2007-02-01 00:00:00
abstract：OBJECTIVE:This article evaluates patients with essential thrombocythemia (ET) to determine whether the V617F mutation in the JAK2 gene affects platelet hemostatic and adhesive molecules, platelet-polymorphonuclear leukocyte (PMN) interactions, and PMN-activation characteristics, as well as plasma hypercoagulation marke...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.01.053
更新日期：2007-05-01 00:00:00
abstract：:Clonal lines of mouse inducer ly1+ly2- inducer T-lymphocytes that depend for growth upon interleukin-2 have been demonstrated to produce a factor that stimulates colony formation by bone marrow granulocyte-macrophage (GM-CFUc) progenitor cells and replication of factor-dependent mast cell/basophil and multipotential h...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-05-01 00:00:00
abstract：:The renal tumor RCC-3-JCK, when transplanted into immunodeficient mice, caused an erythrocytic polycythemia. When grown in culture, the tumor cells secreted a substance into the culture medium that chromatographed by size-exclusion high-performance liquid chromatography similarly to purified human erythropoietin (Ep) ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：OBJECTIVE:The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear. Here we examined the role of Ink4b in blood cell formation using Ink4b-defi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.11.005
更新日期：2007-03-01 00:00:00
abstract：OBJECTIVE:alpha4 Integrins are major players in lymphoid cell trafficking and immune responses. However, their importance in lymphoid reconstitution and function, studied by antibody blockade or in genetic models of chimeric animals with alpha4(KO) embryonic stem (ES) cells, competitive repopulation experiments with fe...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.03.008
更新日期：2008-08-01 00:00:00
abstract：OBJECTIVE:To design a culture method allowing the quantitative and qualitative analysis of terminal erythroid differentiation. METHODS:Primary erythroid progenitors derived either from mouse tissues or from human umbilical cord blood were differentiated using hanging drop cultures and compared to methylcellulose cultu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.06.014
更新日期：2005-10-01 00:00:00
abstract：:The transcription factor SCL is critically required for establishing hematopoiesis and for proper endothelial development, but not for maintenance of hematopoietic stem cells or endothelial cells in the adult. Conflicting data exists regarding the developmental function of SCL, namely, whether it acts as a master regu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.07.005
更新日期：2008-12-01 00:00:00
abstract：OBJECTIVE:Granulocyte colony-stimulating factor (G-CSF) is used to boost granulocyte counts in immunocompromised patients, but its effects on the immune system may be counterproductive. We tested the hypothesis that G-CSF-mobilized peripheral blood stem cell (PBSC) products are immunologically downregulated based on ge...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.06.001
更新日期：2007-09-01 00:00:00
abstract：:Infusion of large numbers of donor regulatory T cells (Tregs) is an effective approach to suppress graft-versus-host disease (GvHD). We have reported previously that enhancing the killing activity of CD25(+) Tregs by decoration with short-lived Fas-ligand (FasL) protein (killer Tregs) is effective in abrogation of aut...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.04.016
更新日期：2013-10-01 00:00:00
abstract：:This review of adjunctive therapy with subcutaneous granulocyte-colony stimulating factor (G-CSF) to patients with acute myocardial infarction (AMI) focus on the cardioprotective effects and potential mechanisms of G-CSF and discuss the therapeutic potential of G-CSF. All clinical trials published in peer-reviewed jou...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2008.01.010
更新日期：2008-06-01 00:00:00
abstract：:The expression of exogenous genes in long-lived primary T cells is potentially beneficial for the treatment of various diseases including cancer, AIDS, genetic defects of the lymphoid compartment, and systemic enzyme deficiencies such as hemophilia. One approach for genetic modification of T cells is to introduce ther...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:In a previous report, we described a method to generate cell lines derived from stromal colonies (colony-derived cell lines [CDCL]). In a first step, colonies were obtained from plating cells from adherent layers of human long-term bone marrow cultures (LTBMC) in methyl-cellulose in the presence of interleukin-1 beta ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-02-01 00:00:00
abstract：:We analyzed the accessory function of malignant B cells from non-Hodgkin's lymphomas (NHLs). Among the 70 samples of malignant B cells included, four patterns of expression of the costimulatory molecules CD80 and CD86 were distinguished (+/+, +/-, -/+ and -/-). In two-thirds of the cases, CD80, CD86, or both were expr...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(98)00059-9
更新日期：1999-03-01 00:00:00
abstract：OBJECTIVE:We previously demonstrated the presence of nucleoside diphosphate kinase NDPK/NM23 in normal human plasma. It also was reported that extracellular NM23 could inhibit differentiation of certain hematopoietic cell lines. We further investigated the extracellular effect of NM23 on hematopoiesis by adding recombi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00809-3
更新日期：2002-07-01 00:00:00
abstract：OBJECTIVE:Adult T-cell leukemia (ATL) is a mature CD4(+) T-cell malignancy caused by infection with human T-lymphotrophic virus type-1 and is associated with a marked hypercalcemia in many patients. Recently, it has been proposed that macrophage inflammatory protein-1alpha (MIP-1alpha) is the clinical hallmark of hyper...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.11.013
更新日期：2008-04-01 00:00:00
abstract：:Chloramphenicol, an antibiotic associated with reversible bone marrow suppression and fatal aplastic anemia, was found to increase human bone marrow granulocyte-macrophage colonies (CFU-GM) in vitro. Maximal stimulation was at a concentration of 1.0 micrograms/ml (3.1 microM), with inhibition at concentrations greater...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-02-01 00:00:00
abstract：:Sphingosine, a sphingolipid breakdown product, has been proposed as an apoptosis-inducing agent. In this study, we examined the effect of sphingosine in bcl-2-overexpressing cells compared with cells that do not express the bcl-2 gene. The human erythroleukemic cell line TF1, which lacks bcl-2 expression, was easily i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-11-01 00:00:00
