Abstract:
OBJECTIVE:Our laboratory reported that the angiotensin converting enzyme inhibitor captopril improves erythroid recovery from total body irradiation (TBI) in mice when administered after irradiation. However, captopril administered before TBI attenuates erythroid recovery. Here we investigate captopril and radiation regulation of erythropoietin (EPO) and thrombopoietin (TPO), key effectors of erythroid progenitor proliferation and differentiation. MATERIALS AND METHODS:C57BL/6 mice, nonirradiated or exposed to 7.5 Gy TBI ((60)Co, 0.6 Gy/min) were untreated or administered captopril. Plasma EPO and TPO levels were measured by enzyme-linked immunosorbent assay. Gene expression of EPO was determined by quantitative reverse transcription polymerase chain reaction. The hypoxia-inducible factors (HIF)-1α and -2α were measured by immunoblotting. RESULTS:In nonirradiated mice, continuous captopril administration in the water transiently reduced reticulocytes and red blood cells after 7 and 10 days, respectively. EPO plasma levels and gene expression were reduced below detectable limits after 2 days of captopril treatment, but recovered within 7 days. HIF-1α and HIF-2α were activated preceding reticulocyte and red blood cell recovery. TBI, which ablates early and late-stage erythroid progenitors, activated both HIFs and increased EPO and TPO. Captopril treatment postirradiation suppressed radiation-induced HIF activation and EPO expression. In contrast, captopril administration for 7 days before TBI resulted in earlier EPO induction and activation. Captopril treatment lowered TPO levels in nonirradiated mice, but had minimal effects on radiation-induced TPO. CONCLUSIONS:In nonirradiated mice, captopril biphasically regulates EPO via HIF activation. TBI ablates erythroid progenitors, resulting in hypoxia, HIF activation, and increased EPO expression that are modulated by captopril treatment. These data suggest that short-term suppression of radiation-induced EPO immediately after TBI is favorable for erythroid recovery.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Barshishat-Kupper M,Mungunsukh O,Tipton AJ,McCart EA,Panganiban RA,Davis TA,Landauer MR,Day RMdoi
10.1016/j.exphem.2010.12.002subject
Has Abstractpub_date
2011-03-01 00:00:00pages
293-304issue
3eissn
0301-472Xissn
1873-2399pii
S0301-472X(10)00597-7journal_volume
39pub_type
杂志文章abstract::A human acute myelomonocytic leukemia cell line, KBM-3, was developed to study the pathophysiology of human acute myeloid leukemia. This cell line was characterized by morphology, immunophenotype, Giemsa-banding pattern, in vitro proliferation capacity, and tumorigenicity in nude mice. The KBM-3 cell line was establis...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract:OBJECTIVE:Preservation of hematopoietic stem and progenitor cells from early radiation-induced apoptosis is the rationale for emergency antiapoptotic cytokine therapy (EACK) after radiation accidents. This strategy is based on the combination of stem cell factor + Flt3-ligand + thrombopoietin + interleukin 3 (SFT3). Th...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.04.017
更新日期:2007-08-01 00:00:00
abstract::Both stimulatory (CSA) and inhibitory (INH) factors may contribute to hematopoietic regulation, but little is known about how their physiologic balance is maintained. Previously we have shown that antigen-defined fibroblastoid cells cultured from rat lung (ST3-/ST4+) constitutively produce INH, and those derived from ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::Protein kinase activities are involved in cellular proliferation and differentiation, and inhibitors of these activities are useful for studying the mechanisms of induction of differentiation. We found that staurosporine, an inhibitor of protein kinase activities, induced morphological differentiation of human myelobl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract:OBJECTIVE:Thrombopoietin stimulates megakaryopoiesis and platelet production by binding to its receptor, Mpl, on hematopoietic progenitor cells. Previously, a murine VB22B minibody for Mpl was shown to stimulate megakaryocyte colony formation in vitro and increase the platelet count in cynomolgus monkeys. In this study...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2011.05.001
更新日期:2011-08-01 00:00:00
abstract:OBJECTIVE:Hematopoietic progenitor cells are a promising source for generation of genetically modified dendritic cells. A prerequisite for using these cells in therapeutic approaches is stable vector-mediated transgene expression during and after cell maturation. We investigated the expression of enhanced green fluores...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00778-0
更新日期:2002-02-01 00:00:00
abstract::Addition of serum or plasma from many species increased the number and size of neutrophilic granulocyte and macrophage colonies formed in vitro by mouse bone marrow cells after stimulation by a variety of preparations containing colony stimulating factor (CSF). The active factor in serum was heat-labile, non-dialyzabl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1975-08-01 00:00:00
abstract::Lymphatic leukemia L1210-bearing semisyngeneic Balb/c x DBA/2Wf F1 (CD2F1) mice were subjected to chemoradiotherapy (2 x 100 mg/kg of cyclophosphamide i.p. and 1000 cGy of total body irradiation) and reconstitution with 10(7) syngeneic bone marrow cells i.v. The bone marrow obtained from leukemic mice was previously e...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::The statistical distribution of colony counts in the spleen colony assay was determined in C57BL/6 and C3H mice under varying conditions of the assay procedure. Assay mice were given syngeneic bone marrow cells from normal or irradiated donors. The mice were injected intravenously with marrow cells either immediately ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-11-01 00:00:00
abstract::Bone marrow cell responses to therapeutic doses of cis-diamminedichloroplatinum (II) (Cis-Pt) were evaluated in female C57B1/6 mice by determining bone marrow cellularity and content of transplantable colony forming units (CFUS) after treatment. Although limitation on the dosage of Cis-Pt is generally considered to be...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00
abstract::We performed the present study to define the in vitro hemopoietic activity of murine recombinant (r) granulocyte colony-stimulating factor (G-CSF) using murine hemopoietic culture systems of normal bone marrow cells, fetal liver cells, and spleen cells of 5-fluorouracil (FU)-treated mice. Recombinant G-CSF supported o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Mammalian erythroblasts undergo enucleation through a process thought to be similar to cytokinesis. Microtubule-organizing centers (MTOCs) mediate organization of the mitotic spindle apparatus that separates the chromosomes during mitosis and are known to be crucial for proper cytokinesis. However, the role of MTOCs i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.12.003
更新日期:2016-04-01 00:00:00
abstract::Classical studies of the developing embryo first suggested the existence of the hemangioblast, a precursor cell with the potential to differentiate into both blood and blood vessels. Several lines of investigation demonstrated that many of the genes activated during early hematopoietic development are also expressed i...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2003.07.001
更新日期:2003-11-01 00:00:00
abstract::An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a co...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the effect of CF101, a synthetic agonist to the A3 adenosine receptor (A3AR), on the production of granulocyte colony-stimulating factor (G-CSF). The ability of CF101 to act as a myeloprotective agent in chemotherapy-treated mice was tested. METHODS:CF101 was administere...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00962-1
更新日期:2002-12-01 00:00:00
abstract::The influence of erythrocytes, extracts of erythrocytes and hemin was assessed on colony formation in vitro by human bone marrow multipotential (CFUGEMM), erythroid (BFUE) and granulocyte-macrophage (CFUGM) progenitor cells. Colony formation by CFUGEMM and BFUE present in the low density (less than 1.077 g/cm3) fracti...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract:OBJECTIVES:To identify the regulatory sequences driving Gata1 expression in conventional dendritic cells (cDC). MATERIALS AND METHODS:The number and expression levels of Gata1, Gata1-target genes and hypersensitive site (HS) 2 (the eosinophil-specific enhancer)-driven green fluorescent protein (GFP) reporter of cDCs f...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.006
更新日期:2010-06-01 00:00:00
abstract::A most stringent test for the non-identity of biologically active materials is provided by the techniques used for parallel line type bioassay of these materials. We have studied commercially available GCT conditioned medium using a parallel line type biological assay for granulocyte-macrophage colony stimulating fact...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-07-01 00:00:00
abstract:OBJECTIVE:The cause of delayed hematopoietic reconstitution after umbilical cord blood transplantation (UCBT) remains controversial. We hypothesized that hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the homing-related molecules responsible for their slow engraftment. MATERIALS AND METHODS...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2003.08.016
更新日期:2003-12-01 00:00:00
abstract::The heat sensitivity at 42 degrees, 43 degrees and 44 degrees C of various hematopoietic subsets in murine bone marrow (MRA, CFU-S-12, CFU-S-8, CFU-GM, BFU-E and CFU-E) was investigated in order to determine whether there is a relationship between heat sensitivity and the position of cells within the stem cell hierarc...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract:OBJECTIVE:Patients with myelodysplasia (MDS) show a disturbed production of ROS in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) in granulocyte-macrophage colony-stimulating factor (GM-CSF)-primed neutrophils. Because generation of ROS is mediated by the NADPH oxidase complex, a component of which is...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00188-7
更新日期:2003-09-01 00:00:00
abstract::CD34 is a cell-surface glycoprotein expressed in a developmental, stage-specific manner by bone marrow stem and progenitor cells. In this study we explored a possible role for c-Myb in CD34 regulation during developmental hematopoiesis. The results indicate that c-Myb can induce CD34 expression in hematopoietic and no...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract::A right atrial catheter was implanted into 15 patients undergoing bone marrow transplantation as a treatment for acute leukemia. The catheter remained in position for 79 +/- 34 days. No catheter-related septicemia was observed. It appears that this catheter is helpful in supporting bone marrow transplant recipients. ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-08-01 00:00:00
abstract::Normal and myeloid leukemic spleen cells from RF mice were cultured in vitro in plasma clots. In situ histochemical staining and karyotypic analysis of the colonies formed in the clot revealed that the colonies produced by leukemic and normal progenitors were indistinguishable morphologically and cytochemically. Colon...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-02-01 00:00:00
abstract::Delayed platelet recovery and altered marrow megakaryocytopoiesis was observed in highly irradiated mice following transplantation with 1000 lineage-negative, stem cell antigen-positive (Lin-Sca-1+) cells. Thirty days after transplantation, the mice were thrombocytopenic. Normal platelet levels were reestablished by 9...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::Data in this report determined the effect of a single injection of recombinant interleukin 1 alpha (rIL-1) prior to irradiation of B6D2F1 mice on the recovery of colony-forming cells (CFC) at early and late times after sublethal and lethal doses of radiation. Injection of rIL-1 promoted an earlier recovery of mature c...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Quantitative measurements on the haemopoiedic systems of SAS/4, 3H and RFM mice have been used to calculate the distribution and population sizes of haemopoietic cells in the bone marrow, spleen and peripheral blood. Considerable strain differences have been found in the sizes of haemopioetic stem cell populations and...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1975-06-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to investigate the effects of interleukin-2 (IL-2) gene-transduced hematopoietic progenitor cells or cytotoxic function and systemic toxicity following syngeneic bone marrow transplantation. MATERIAL AND METHODS:Marrow of 5-fluorouracil pretreated donor mice were transfected wit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00487-2
更新日期:2000-08-01 00:00:00
abstract:OBJECTIVE:We previously demonstrated a silencing role for signal transducers and activators of transcription 3 (STAT3) in gamma-globin gene regulation in primary erythroid cells. Recently, GATA-1, a key transcription factor involved in hematopoietic cell development, was shown to directly inhibit STAT3 activity in vivo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.05.004
更新日期:2009-08-01 00:00:00