Abstract:
:The fate of hematopoietic progenitor cells (HPCs) in the bone marrow (BM) microenvironment is determined by two different interactions: 1) they adhere (via integrins) to both extracellular matrix molecules and BM stromal cells; and 2) stromal cells produce cytokines that influence their survival, proliferation, differentiation, and mobilization. The ligands for the protein tyrosine kinase receptors c-KIT and FLT3/FLK2, stem cell factor (SCF), and FL are produced by BM stromal cells and are known to affect several facets of hematopoiesis. We studied another protein tyrosine kinase receptor, c-MET, and its ligand hepatocyte growth factor (HGF), also known as scatter factor (SF), which play a similar role in hematopoiesis. c-MET mRNA is expressed in immature human BM HPCs (CD34+CD33- or CD34+CD38-), but not in more mature HPCs (CD34+CD33+ or CD34+CD38+). The ligand HGF/SF is predominantly produced by BM stromal cells at both the mRNA and protein levels. We confirmed functionally that HGF/SF alone has no effect on proliferation of HPCs, but that when combined with granulocyte/macrophage colony-stimulating factor (GM-CSF) or interleukin-3 it acts as a synergistic proliferative factor, although not as potently as kit-ligand or FLT-3/FLK-2 ligand. Furthermore, HGF/SF promotes adhesion of HPCs to immobilized fibronectin. HGF/SF-induced adhesion to fibronectin is probably caused by activation of the integrins alpha4beta1 and alpha5beta1, insofar as we were able to block this interaction by using monoclonal blocking antibodies directed against these integrin subunits. Addition of the tyrosine-phosphorylation inhibitor genistein inhibited HGF/SF-induced adhesion, supporting the idea that HGF/SF-induced effects are the result of signaling via the receptor c-MET after ligand binding. The enhanced adhesion of HGF/SF to fibronectin proved to be beneficial for the maintenance of the colony-forming potential of HPCs. HGF/SF alone and especially in combination with fibronectin prolongs survival of GM colony-forming cells in liquid culture. Our data indicate that HGF/SF is a polyfunctional cytokine in the BM microenvironment. It is produced by human BM stromal cells and directly or indirectly promotes proliferation, adhesion, and survival of human HPCs.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Weimar IS,Miranda N,Muller EJ,Hekman A,Kerst JM,de Gast GC,Gerritsen WRsubject
Has Abstractpub_date
1998-08-01 00:00:00pages
885-94issue
9eissn
0301-472Xissn
1873-2399journal_volume
26pub_type
杂志文章abstract::Human cord blood or bone marrow cells expressing the CD34 surface antigen include a population of pluripotent progenitors. We identified and isolated a subpopulation of cells coexpressing CD34 and c-kit, a transmembrane receptor with tyrosine kinase activity. Novel monoclonal antibodies (16A6, 14A3, 3D6) directed agai...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::We created fully and stable xenogeneic hematopoietic chimeras in "poorly concordant" rat-mouse strain combinations defined by their high histocompatibility-antigen disparity and by the high titer of mouse-serum natural cytotoxic antibodies (NcAb) to rat donor bone marrow cells (BMC). Recipients were adult male (C57BL/...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::Mammalian hemopoiesis results from a complex interaction between hemopoietic progenitor cells, stromal cells and extracellular matrix components, orchestrated by specific glycoprotein growth factors. Recently, these growth factors have been shown to possess an important function, apart from stimulation of proliferatio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Marrow obtained from mice (referred to as [X + BM] mice) 3 months after gamma-irradiation (9 Gy) and bone marrow inoculation (0.1 femur equivalents) showed a reduced capacity to reconstitute hemopoiesis of irradiated mice and an increased sensitivity to 5-fluorouracil. Sorting of marrow from (X + BM) mice on the basis...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Cells of two transplantable leukemias of mice, one myeloid and one lymphoid, were labeled with 51Cr in order to follow their distribution in hemopoietic and parenchymatous organs and blood of syngeneic recipients. Distribution of myeloid leukemia cells was compared with that of regenerating bone marrow cells and norma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract::The more mature erythroid progenitor assayable in vitro, the colony-forming unit-erythroid (CFU-E), is normally found in the bone marrow (BM) but is virtually absent from peripheral blood (PB), unlike the more immature progenitor, the burst-forming unit-erythroid (BFU-E). We report on the detection of CFU-E in the PB ...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1995-12-01 00:00:00
abstract::Fractionated whole body irradiation induces thymic lymphomas in C57 BL/Ka mice after 6-12 months. A graft of normal congenic bone marrow cells immediately after the last irradiation prevents the development of lymphomas by inducing the disappearance of preleukemic cells. When such a graft is performed one month later,...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::We have attempted to evaluate in vivo effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on acute radiation hematopoietic injury in mice. BDF1 mice, irradiated with 7.5-Gy x-rays, were injected i.p. twice daily for 10 days with 10(5) U recombinant hum...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-09-01 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:OBJECTIVE:Although all-trans retinoic acid (ATRA) can bring about complete remission of acute promyelocytic leukemia (APL), the incidence of early recurrence is considerably high. Thus, chemotherapeutic agents, such as anthracycline agents or cytosine arabinoside (AraC), are generally co-administered with ATRA. The the...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00905-0
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVE:To investigate whether Flk1(+)CD31(-)CD34(-) cells isolated from fetal bone marrow (BM) have characteristics of hemangioblasts, i.e., progenitors of endothelial and hematopoietic cells. MATERIALS AND METHODS:Mononuclear cells from fetal BM were negatively sorted by CD45, GlyA, and CD34 micromagnetic beads, t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00087-0
更新日期:2003-07-01 00:00:00
abstract:OBJECTIVE:Stem cell transplantation has a place in the management of many patients with hematological disorders, but is no longer the final and definitive treatment for most of these individuals. The relapsing patient may be offered further therapy, and evaluating the contribution of the treatments available has become...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.06.007
更新日期:2008-11-01 00:00:00
abstract::The modulatory effect of 1,25 dihydroxyvitamin D3 (vit D) and 13 cis retinoic acid (retinoic acid) on the growth and differentiation of normal human pluripotent stem cell, erythroid, and myeloid progenitor cell growth was studied using semisolid methylcellulose clonal assay. Dose response curves showed that maximal in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results r...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.08.028
更新日期:2008-01-01 00:00:00
abstract::Addition of carbamylcholine, a cholinergic analogue, to bone marrow cultures enhanced megakaryocytic and granulocytic growth by 60% and 42%, respectively. When carbamylcholine was added to spleen cells cultured in the presence of pokeweed mitogen, the resulting conditioned medium (PWM-SCM) increased the number of mega...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Mice with the nu mutation have been shown to have a reduced incidence of spleen colony-forming units (CFU-S), with a higher variability between individual mice compared to +/+ mice. The presence of these defects also in nu/+ mice indicates that this mutation is a codominant trait and that the hematopoietic changes may...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract:OBJECTIVE:The Hedgehog family of intercellular proteins has a crucial role in embryonic development. Recent experimental data suggests that the Hedgehog pathway may play a role in early hematopoiesis and angiogenesis. Stem cell leukemia (SCL), a basic helix-loop-helix (bHLH) transcription factor, is essential for the s...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.07.019
更新日期:2006-12-01 00:00:00
abstract::Tumor necrosis factor alpha (TNFalpha) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RII) receptor is responsible for the TNFalpha-induced inhibition of hepatic Epo synth...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00054-x
更新日期:1999-02-01 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:OBJECTIVES:Processing of epigenomic transcriptional information by cell cycle phase G(1) and decision-making at checkpoint G(1)/S are the final organizational steps preceding gene replication in transcriptional reorientation programs (i.e., switches from proliferation to cycle arrest and neoplastic transformation). Fur...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2008.07.009
更新日期:2008-11-01 00:00:00
abstract:OBJECTIVE:Recognition of E- and P-selectins on vascular endothelium by their leukocyte glycoprotein counterreceptor P-selectin glycoprotein ligand-1 (PSGL-1) initiates and sustains leukocyte rolling, culminating in extravasation of lymphocytes from blood into organs. PSGL-1 is rendered functional by terminal glycosylat...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.08.003
更新日期:2005-12-01 00:00:00
abstract::In this study, we have used the sublethally irradiated rat as a model to examine the relationship between platelet count and the plasma level of megakaryocyte growth-promoting activity (Meg-GPA) assayed in vitro. Meg-GPA of irradiated rats whose platelet counts were maintained by platelet transfusions was compared to ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::A functional method for estimation of plasminogen activator (PA) activity is described. The end-point method follows the PA-dependent conversion of the inactive plasminogen to the potent protease plasmin. The formation of plasmin is monitored by its activity on 14C-globin to form acid-soluble radioactive products. The...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::The tumor suppressor p53 is thought to play a role in megakaryocyte (MK) development. To assess the influence of the p53 regulatory pathway further, we studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53 by preventing its interaction with MDM2, on normal megakaryocytopoiesis and platelet ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.11.012
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:About one third of patients requiring allogeneic hematopoetic stem cell transplantation (HSCT) would not find a matched sibling or alternative donor. Allogeneic HSCT from matched unrelated and mismatched donors carries an increased risk of graft-vs-host disease (GVHD) and transplant-related mortality (TRM). ...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2008.03.011
更新日期:2008-08-01 00:00:00
abstract:OBJECTIVE:CD34(+) cells, present within the bone marrow, have previously been shown to possess pancreatic endocrine potential. Based on this observation, we explored the capacity of CD34(+) cells derived in culture from the differentiation of human embryonic stem cells (hESC), for their in vivo pancreatic endocrine cap...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.002
更新日期:2010-06-01 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::The granulocyte defects of Chediak-Higashi syndrome (CHS) include neutropenia, characteristic giant lysosomal granule morphology, and functionally abnormal cell motility, degranulation, and bacterial killing. Findings of elevated levels of adenosine 3', 5' cyclic monophosphate nucleotide (cAMP) and of concanavalin A (...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::The myeloproliferative neoplasms (MPNs) are somatic mutation-driven hematologic malignancies characterized by bone marrow fibrosis and the accumulation of atypical megakaryocytes with reduced polyploidization in the primary myelofibrosis subtype of the MPNs. Increasing evidence points to a dominant role of abnormal me...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2016.12.007
更新日期:2017-04-01 00:00:00
abstract::Pretreatment of mice with 5-fluorouracil (5-FU) depletes total marrow cellularity but leaves a residual population of cells with enhanced regenerative capability. Using the long-term Dexter liquid culture system, we studied the effects of 5-FU on murine marrow cells and their production of pluripotent stem cells (CFU-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00