Abstract:
OBJECTIVES:Macrophage inflammatory protein-1alpha (MIP-1alpha), an osteoclast (OCL) stimulatory factor produced by primary multiple myeloma (MM) cells, increases bone destruction and tumor burden in murine models of MM. Several chemokine receptors (CCR1, CCR5, and CCR9) mediate the effects of MIP-1alpha. In this study, we determined which of these mediates the effects of MIP-1alpha on human OCL formation and myeloma cells. METHODS:We employed RT-PCR analysis, neutralizing antibodies to CCR1 and CCR5 as well as a CCR1-specific antagonist and OCL formation assays to identify the MIP-1alpha receptors involved in MIP-1alpha's effects on myeloma cells and OCL formation. RESULTS:RT-PCR analysis demonstrated that both CCR1 and CCR5 were expressed by highly purified human OCL precursors, myeloma cell lines, and purified marrow plasma cells from MM patients. Neutralizing antibodies to CCR1 or CCR5 inhibited MIP-1alpha-induced OCL formation. Furthermore, monocyte chemotactic protein-3 (MCP-3), which binds CCR1 but not CCR5 and the CCR1-specific antagonist, BX471, markedly inhibited OCL formation stimulated with MIP-1alpha. Anti-CCR1, anti-CCR5, or BX471 also inhibited the upregulation of beta1 integrin mRNA in myeloma cells induced by MIP-1alpha, as well as the adherence of myeloma cells to stromal cells and IL-6 production by stromal cells in response to myeloma cells. CONCLUSION:These data demonstrate that MIP-1alpha utilizes either CCR1 or CCR5 for its effects on OCL formation and myeloma cells, and that blocking either CCR1 or CCR5 inhibits OCL formation and myeloma cell adhesion to stromal cells.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Oba Y,Lee JW,Ehrlich LA,Chung HY,Jelinek DF,Callander NS,Horuk R,Choi SJ,Roodman GDdoi
10.1016/j.exphem.2004.11.015keywords:
subject
Has Abstractpub_date
2005-03-01 00:00:00pages
272-8issue
3eissn
0301-472Xissn
1873-2399pii
S0301-472X(04)00433-3journal_volume
33pub_type
杂志文章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:OBJECTIVE:Common marmosets are considered experimental animals of primates useful for medical research. We developed several monoclonal antibodies (mAbs) directed to CD molecules to gain initial insight into the immune and hematopoietic systems of this organism, and analyzed the basic cellularity and characters of marm...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.08.003
更新日期:2009-11-01 00:00:00
abstract::The four existing animal models of cyclic hematopoiesis are briefly described. The unusual erythropoietin (Ep) responses of the W/Wv mouse, the Sl/Sld mouse, and cyclic hematopoietic dog are reviewed. The facts reviewed indicate that the bone marrow itself is capable of influencing regulatory events of hematopoiesis. ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-08-01 00:00:00
abstract:OBJECTIVE:Differentiation-inducing therapy by agents such as 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) represents a useful approach for the treatment of acute myelogenous leukemia (AML). We previously showed that Gemini-23-yne-26,27-hexafluoro-D(3) inhibited the proliferation of MCF-7 breast cancer cells in associat...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.020
更新日期:2010-08-01 00:00:00
abstract::The effect on marrow myeloblast colony formation in blood from nine patients with acute myeloid leukemia was studied by using three recombinant-DNA-derived human leukocyte interferons (IFN alpha 2, IFN alpha-A, and IFN alpha-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFN alpha resulte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract:OBJECTIVE:It has been shown previously that infection with diverse viruses induces alterations in bone marrow lineage-specific progenitor cells. As complications arising from secondary bacterial infections can adversely affect the host, we investigated whether virally induced hematological alterations could contribute ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.09.005
更新日期:2005-12-01 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::The course of development of graft-versus-host reactions (GVHR) following lethal irradiation was compared in two mouse donor-host combinations disparate at non H-2 loci alone or associated to H-2 complex. The pathogenesis of these reactions was very different (mortality rates faster in the second situation for example...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-05-01 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::Certain biological effects exerted by 4-hydroperoxycyclophosphamide and by 2,4-tetrahydrocyclohexylamine (ASTA-Z-7557), utilized in vitro in the therapy of leukemias and lymphomas to eliminate the occult tumor cells in autologous marrow transplantations, were studied in human lymphocytes cultured in vitro. The data sh...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-11-01 00:00:00
abstract::A modification of the fluorescence-activated cell sorter (FACS) was used to rapidly and reliably study the clonal proliferation of single hemopoietic cells. Murine FDC-P1 and human cord blood progenitor cells were examined for their ability to proliferate from single cells in 96-well microtiter plates containing agar ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::More than 2million human erythroblasts extrude their nuclei every second in bone marrow under hypoxic conditions (<7% O2). Enucleation requires specific signal transduction pathways and the local assembly of contractile actomyosin rings. However, the energy source driving these events has not yet been identified. We e...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.02.004
更新日期:2019-04-01 00:00:00
abstract::The effects of a single injection of hemin on murine marrow BFU-E and CFU-S were assessed to determine whether hemin is as effective in augmenting primitive (day 7) BFU-E levels in situ as it is in vitro and to assess hemin's action on transplantable pluripotent stem cells (CFU-S). The results show that hemin exerts a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::A cell line (LAMA-84) has been established from the blood of a patient with chronic myeloid leukemia in acute phase. LAMA-84 cells retained the patient's chromosome abnormalities, i.e., triplication of all chromosomes except chromosome 18, the presence of Philadelphia (Ph) chromosome in 4-5 copies, and the presence of...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::We have examined the capacity of highly purified human CD34+ marrow cell isolates from unrelated, HLA-mismatched donors to establish in vitro hematopoiesis on recipient marrow stromal cells in 2-stage hematopoietic long-term marrow cultures (H-LTMC). HLA-typing of both peripheral blood mononuclear cells and CD34+ marr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract:OBJECTIVE:Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed by the malignant cells of about 30% of cases of Hodgkin's lymphoma (HL) and is therefore a potential target for immune attack. Given the predominantly immunosuppressive nature of HL infiltrating lymphocytes (HLILs) and the ability ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.01.030
更新日期:2007-04-01 00:00:00
abstract:OBJECTIVE:Donor lymphocyte transfusions (DLT) are effective in the treatment of leukemia after allogeneic stem cell transplantation. Graft-vs-host-disease (GVHD) is the major risk factor of DLT. In dog leukocyte antigen (DLA)-identical littermate dogs, DLT given within 3 weeks after transplantation of marrow depleted o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.05.001
更新日期:2009-08-01 00:00:00
abstract::The first blood cells observed in the embryo are large nucleated erythroblasts generated in blood islands of the extraembryonic yolk sac. These unique red cells have been termed primitive because of their resemblance to nucleated erythroblasts of nonmammalian species. It is now widely assumed that hematopoiesis in the...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2005.06.012
更新日期:2005-09-01 00:00:00
abstract::Colony formation by megakaryocyte (MK) progenitors was studied in 36 normal individuals and in 26 patients with primary thrombocythemia (PT) using an improved plasma clot cloning system. MK colonies were identified by immunoperoxidase staining using a monoclonal antibody against human platelet glycoprotein IIb/IIIa co...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::Activation of the N-ras gene via coding region mutations has been previously documented in 25% of patients with acute myeloid leukemia (AML). Since overexpression of normal N-ras is also transforming in vitro, the N-ras promoter of AML patients was analyzed for the presence of promoter mutations that may affect expres...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::Sustained NF-κB activation is often observed in acute myeloid leukemia (AML); therefore, proteasome inhibition has been proposed to efficiently target AML cells. In this study, we questioned whether leukemic stem cell-enriched CD34(+) cells are sensitive to the proteasome inhibitor bortezomib. Surprisingly, we observe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.02.002
更新日期:2013-06-01 00:00:00
abstract::Human bone marrow contains plastic-adherent hemopoietic progenitor cells whose plating efficiency is increased by brief (2 h) exposure to methylprednisolone (MP). When subsequently covered with methylcellulose medium, they form colonies of monoblastoid cells. Colony size, but not number, and mature cell production are...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-08-01 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: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:Beta-thalassemia results from beta-globin gene mutations that lead to ineffective erythropoiesis, shortened red cell survival, and anemia. Patients with beta-thalassemia develop iron overload, despite which, hepcidin levels are low. This suggests that hepcidin regulation in beta-thalassemia is more sensitive ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.10.004
更新日期:2009-02-01 00:00:00
abstract::The effect of indomethacin (6 mg/kg daily orally for 2, 3 or 4 days) on myelopoiesis was studied in mice by estimating 1) differential cell counts of bone marrow, 2) proliferation of the CFUC in presence of GM-CSF, 3) proliferative state of CFUC after tritiated thymidine suicide. After 4 days of treatment, a rise in t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-10-01 00:00:00
abstract::Granulocyte colony-stimulating factor (G-CSF) is used routinely in the clinical setting to mobilize hematopoietic stem progenitor cells (HSPCs) into the patient's blood for collection and subsequent transplantation. However, a significant proportion of patients who have previously received chemotherapy or radiotherapy...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2017.05.004
更新日期:2017-08-01 00:00:00
abstract::The pool size of erythroid burst-(BFUe) and colony-forming units (CFUe) has been evaluated in normal or hypoxia-induced polycythemic mice at sequential times after either transfusion or administration of purified erythropoietin (Ep). The present investigations were focused on the in vitro tritiated thymidine (3H-TdR) ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract::The advent of single-cell transcriptomics has led to the proposal of a number of novel high-resolution models for the hematopoietic system. Testing the predictions generated by such models requires cell fate potential assays of matching, single-cell resolution. Here we detail the development of an in vitro high-throug...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.01.005
更新日期:2018-04-01 00:00:00
abstract::Seven patients received cancer chemotherapy with high-dose cyclophosphamide (HD-CTX) associated with either recombinant human granulocyte colony-stimulating factor (rhG-CSF), rh interleukin-3 (rhIL-3), rh granulocyte-macrophage CSF (rhGM-CSF) plus rh erythropoietin (rhEpo), rhIL-3 plus rhGM-CSF, or rhIL-3 plus rhG-CSF...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00