Abstract:
:Peripheral blood progenitor cells (PBPC) mobilized by granulocyte colony-stimulating factor (G-CSF) promptly engraft allogeneic recipients after myeloablative chemotherapy for hematologic malignancies. Surprisingly, no exacerbation of acute graft-vs-host disease has been observed despite a 10-fold higher T-cell content in PBPC compared with bone marrow allografts. Because G-CSF can suppress T-cell proliferation in response to mitogens and enhance their activation-induced apoptosis, we examined the molecular mechanisms underlying G-CSF-induced immune dysfunction. Normal allogeneic lymphocytes were challenged with phytohemagglutinin in the presence of serum collected after G-CSF administration (postG) to healthy PBPC donors, and the expression of key components of the cell cycle and apoptotic machineries was investigated by flow cytometry and Western blotting. Lymphocyte stimulation was associated with collapse of mitochondrial transmembrane potential, hypergeneration of reactive oxygen intermediates, and activation of caspase-3 and DNA fragmentation. Lymphocytes were arrested in a G(1)-like phase of the cell cycle, as measured by G(1)-phase cyclin expression and bromodeoxyuridine (BrdUrd) incorporation. Cell tracking experiments confirmed the occurrence of a lower number of population doublings in postG compared with preG cultures. Unexpectedly, the phosphorylation state of the protein encoded by the retinoblastoma susceptibility gene (pRB) was unaltered in postG cultures, and the inhibition of cell cycle progression occurred without the recruitment of the cyclin-dependent kinase inhibitors p15(INK4B), p16(INK4A), and p27(Kip1). We eventually evaluated the ability of antioxidant/cytoprotectant agents to prevent the G-CSF-induced mitochondrial dysfunction and inhibition of cell cycle progression. Of interest, both N-acetylcysteine and amifostine reduced apoptotic cell death by 45% on average, inhibited the activation/processing of caspase-3, and increased BrdUrd incorporation in postG cultures. Based on these experimental findings, a model is proposed in which T-cell activation in the presence of serum immunoregulatory factor(s) induced by G-CSF is associated with a molecular phenotype mimicking the G(1)-S transition and consisting of pRB phosphorylation, lack of CDKI recruitment, and reduced cyclin-E expression. The putative relationship between lymphocyte mitogenic unresponsiveness and apoptosis induction would occur at the level of key molecules shared by the cell cycle and apoptotic machineries. Whether the G-CSF-mediated modulation of lymphocyte functions in vitro is beneficial in transplantation medicine remains to be determined.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Rutella S,Pierelli L,Rumi C,Bonanno G,Marone M,Sica S,Capoluongo E,Ameglio F,Scambia G,Leone Gdoi
10.1016/s0301-472x(01)00617-8keywords:
subject
Has Abstractpub_date
2001-04-01 00:00:00pages
401-15issue
4eissn
0301-472Xissn
1873-2399pii
S0301-472X(01)00617-8journal_volume
29pub_type
杂志文章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::Remarkable advances have been made in bone marrow transplantation (BMT), which now has become a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency disorders, and autoimmune diseases. Using various animal models, allogeneic BMT has been found to be useful in the treatment of a...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/s0301-472x(01)00645-2
更新日期:2001-06-01 00:00:00
abstract::We evaluated the expansion capacity of untreated and 5-fluorouracil (5-FU)-resistant peripheral blood stem cells (PBSC) after 7-day incubation with interleukin-1 (IL-1) plus IL-3 plus stem cell factor (SCF) or with medium alone. We found a significant increase in the proportion of CD34+ cells in the PBSC fraction resi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Germinal center-associated nuclear protein (GANP) is a unique and multifunctional protein that plays a critical role in cell biology, neurodegenerative disorders, immunohematology, and oncogenesis. GANP is an orthologue of Saccharomyces Sac3, one of the components of the transcription export 2 (TREX-2) complex and a m...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2020.08.007
更新日期:2020-10-01 00:00:00
abstract::We have previously shown that CD33- CD34+ human marrow cells are capable of giving rise to colony-forming cells (CFC) in long-term marrow culture (LTMC) but are mainly depleted of progenitors that directly form colonies in semi-solid media. In contrast, the CD33+ CD34+ population contains most of the CFC but not the p...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::Serial clonogenicity studies employing an agar CFUc culture assay are being performed on cells from CML patients to determine if clonal growth, 3HTdR suicide indices (SI) and in vitro busulfan sensitivity are of prognostic significance in predicting blastic transformation. Initial studies performed on specimens obtain...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-08-01 00:00:00
abstract:OBJECTIVE:The advantage of recipient hematopoiesis over that of xenogeneic donors poses a fundamental obstacle to the induction of xenograft tolerance through mixed hematopoietic chimerism. Here we explore the role of beta1 integrins in maintenance of human vs porcine hematopoiesis within a human hematopoietic environm...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.11.011
更新日期:2005-03-01 00:00:00
abstract::The extent of incorporation of bromodeoxyuridine (BrdUrd) into DNA of different types of hematopoietic stem cells assayed in vivo and of progenitor cells assayed in vitro was determined after continuous infusion of BrdUrd into mice for either four or seven days. Cells surviving subsequent exposure to 320 nm ultraviole...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-10-01 00:00:00
abstract::A method for growing erythroid bursts from rat bone marrow cells is presented. The methylcellulose culture technique with rat spleen-conditioned medium was used. Successful growth of rat BFU-E was obtained with 20% fetal bovine serum when anemic rat plasma was used as the source of erythropoietin. Plating efficiency w...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract:OBJECTIVE:The primary objective of this study was to identify and clone the first nonmammalian thrombopoietin (TPO), chicken TPO, and its receptor c-Mpl for the purpose of characterizing their activities both in vitro and in vivo. MATERIALS AND METHODS:Chicken TPO was cloned using the methods of reverse transcriptase ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.12.001
更新日期:2008-04-01 00:00:00
abstract::Heterozygous alpha-thalassemic (Hbath/+) female mice were investigated for the effect of persistent erythropoietic stress on the number of stem cells and progenitor cells along the the erythroid (E), granulocyte-macrophage (GM), and megakaryocyte (Meg) pathways. At the progenitor cell level, compensatory erythropoiesi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::Serum albumin has long been an essential supplement for ex vivo hematopoietic and immune cell cultures. However, serum albumin medium supplements represent a major source of biological contamination in cell cultures and often cause loss of cellular function. As serum albumin exhibits significant batch-to-batch variabi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.11.007
更新日期:2019-12-01 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:OBJECTIVE:Polycythemia rubra vera-1 (PRV-1) is a GPI-linked protein that is expressed on a subgroup of neutrophils. The number of PRV-1-expressing neutrophils increases in pregnancy and sepsis, or after administration of granulocyte colony-stimulating factor. Expression of the PRV-1 gene is also increased in patients w...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.09.008
更新日期:2007-11-01 00:00:00
abstract::Initiation of DNA synthesis by recombinant colony-stimulating factors (CSFs) was assessed in normal human marrow blast cells isolated by expression of CD34 antigen (tritiated thymidine incorporation). Continuous exposure to CSF was required. A mild increase in DNA synthesis was initiated by granulocyte CSF (G-CSF; gre...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::The osteoclast is a hematopoietic cell derived from CFU-GM and branches from the monocyte-macrophage lineage early during the differentiation process. The marrow microenvironment appears critical for osteoclast formation due to production of RANK ligand, a recently described osteoclast differentiation factor, by marro...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/s0301-472x(99)00061-2
更新日期:1999-08-01 00:00:00
abstract:OBJECTIVE:Progenipoietin-1 is an agonist of both the granulocyte colony-stimulating factor and fetal liver tyrosine kinase-3 receptors capable of inducing the proliferation of multiple hematopoietic cell lineages. The potential of progenipoietin-1 to mobilize transplantable hematopoietic stem cells into the peripheral ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00675-0
更新日期:2001-08-01 00:00:00
abstract:OBJECTIVES:To analyze the consequences of lymphocyte donations on lymphopoiesis in donors having previously undergone hematopoietic stem cell collection for allogeneic stem cell transplantation. METHODS:Repeated analysis of leukocyte subsets in the peripheral blood of 76 hematopoietic stem cell donors undergoing lymph...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.07.021
更新日期:2004-11-01 00:00:00
abstract::Pathogenesis of cytomegalovirus (CMV)-induced myelosuppression is not clearly understood and could be related to a direct toxic effect on the marrow progenitors and/or an alteration of the marrow environment. Myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) were not affected by incubation with...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Septins are a family of filament-forming GTP-binding proteins that serve as scaffolds and diffusion barriers in various cellular processes. Septin 6 is known as a fusion partner of mixed-lineage leukemia in infant acute myeloid leukemia. The occurrence of the fusion gene is associated with a reduced expression of sept...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2017.07.005
更新日期:2017-11-01 00:00:00
abstract::Mast cell (MC)-fibroblast-immunocompetent cell interactions may play a role in the inflammatory and fibrotic processes present in chronic graft-vs.-host disease (cGVHD). Interactions between these cell types were examined in both murine and human cGVHD models. To this purpose, cell supernatants from mice or humans wit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract:OBJECTIVE:In utero hematopoietic cell transplantation (IUHCT) is a non-ablative approach that achieves mixed allogeneic chimerism and donor-specific tolerance. However, clinical application of IUHCT has been limited by minimal engraftment. We have previously demonstrated in the murine model that low-level allogeneic ch...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.11.011
更新日期:2006-03-01 00:00:00
abstract::Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thromboc...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::Peripheral blood lymphocytes obtained at 24-30 months after birth from a male with X-linked severe combined immune deficiency maintained in a gnotobiotic environment were characterized by T and B cell surface markers. A high proportion (55-80 percent) of circulating lymphocytes bore surface IgM as detected by direct i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1976-01-01 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:High-dose radiation exposure induces acute myeloid leukemia (AML) in C3H mice, most of which have a frequent hemizygous deletion around the D2Mit15 marker on chromosome 2. This region includes PU.1, a critical candidate gene for initiation of leukemogenesis. To identify novel cooperative genes with PU.1, rele...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.01.015
更新日期:2008-07-01 00:00:00
abstract:BACKGROUND:Autologous bone marrow transplantation is an important therapy for patients with acute myelogenous leukemia (AML). However, leukemia in the graft may contribute to posttransplant relapse. Treatment of the graft with 4-hydroperoxycyclophosphamide (4HC) is sometimes used to decrease numbers of infused leukemia...
journal_title:Experimental hematology
pub_type: 杂志文章,多中心研究
doi:10.1016/s0301-472x(01)00732-9
更新日期:2001-11-01 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::The immediate hematopoietic response to 3'-azido-3'-deoxythymidine (AZT) was characterized in an unperturbed and regenerating mouse marrow model to identify the in vivo hematopoietic targets of AZT and test whether AZT toxicity is dependent on the proliferative activity of the hematopoietic targets. B6D2F1 mice receiv...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-01-01 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