Thrombopoietin augments stem cell factor-dependent growth of human mast cells from bone marrow multipotential hematopoietic progenitors.

The effects of thrombopoietin (TPO) and/or stem cell factor (SCF) on the development of human mast cells from CD34(+) bone marrow (BM) cells were investigated using a serum-deprived liquid culture system. Mast cells were identified by measurement of intracellular histamine content, immunocytochemical staining, and flow cytometric analysis. Whereas SCF alone generated only a small number of tryptase+ cells, the addition of TPO to the culture containing SCF resulted in an apparent production of mast cells from 3 weeks until at least 15 weeks. Some of the cells reacted with an antichymase monoclonal antibody as well. Based on the effects of growth factor(s) on a later phase of the mast cell growth, TPO may stimulate an early stage of mast cell development in combination with SCF, whereas subsequent growth seems to be supported by SCF alone. Single-cell culture studies indicated that the CD34(+)CD38(-)c-kit+ cells and CD34(+)CD38(+)c-kit+ cells were responsible for the SCF + TPO-dependent mast cell production. Two-step culture assays clearly showed that mast cells originated from multilineage colony-forming cells that had potential to differentiate into neutrophil/mast cell lineages, neutrophil/macrophage/mast cell lineages, or neutrophil/macrophage/mast cell/erythroid lineages. These results suggest that TPO plays an important role in the development of human mast cells from CD34(+) BM cells in concert with SCF, and provide direct evidence of the differentiation into the mast cell lineage of human multipotential BM-derived progenitors.

[1]  K. Koike,et al.  Thrombopoietin enhances the production of myeloid cells, but not megakaryocytes, in juvenile chronic myelogenous leukemia. , 1998, Blood.

[2]  T. Kamijo,et al.  Establishment of a GM‐CSF‐dependent megakaryoblastic cell line with the potential to differentiate into an eosinophilic lineage in response to retinoic acids , 1998, British journal of haematology.

[3]  A. Roberts,et al.  Endogenous Thrombopoietin Levels and Effect of Recombinant Human Thrombopoietin on Megakaryocyte Precursors in Term and Preterm Babies , 1998, Pediatric Research.

[4]  H. Miyazaki,et al.  Thrombopoietin, steel factor and the ligand for flt3/flk2 interact to stimulate the proliferation of human hematopoietic progenitors in culture. , 1997, International journal of hematology.

[5]  H. Miyazaki,et al.  Megakaryocytes derived from CD34‐positive cord blood cells produce interleukin‐8 , 1997, British journal of haematology.

[6]  A. Guerriero,et al.  Thrombopoietin is synthesized by bone marrow stromal cells. , 1997, Blood.

[7]  L. Schwartz,et al.  Recombinant human granulocyte-macrophage colony-stimulating factor (CSF), but not recombinant human granulocyte CSF, down-regulates the recombinant human stem cell factor-dependent differentiation of human fetal liver-derived mast cells. , 1997, Journal of immunology.

[8]  H. Miyazaki,et al.  Thrombopoietin supports proliferation of human primitive hematopoietic cells in synergy with steel factor and/or interleukin-3. , 1996, Blood.

[9]  K. Matsumoto,et al.  Selective growth of human mast cells induced by Steel factor, IL-6, and prostaglandin E2 from cord blood mononuclear cells. , 1996, Journal of immunology.

[10]  A. Matsumoto,et al.  A sensitive sandwich ELISA for measuring thrombopoietin in human serum: serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders , 1996, British journal of haematology.

[11]  G. Nilsson,et al.  Stem cell factor, but not flt3 ligand, induces differentiation and activation of human mast cells. , 1996, Experimental hematology.

[12]  T. Kamijo,et al.  Aberrant growth of granulocyte-macrophage progenitors in juvenile chronic myelogenous leukemia in serum-free culture. , 1996, Experimental Hematology.

[13]  A. Iwamatsu,et al.  Purification and characterization of thrombopoietin. , 1995, Journal of biochemistry.

[14]  P. Valent,et al.  Origin of human mast cells: development from transplanted hematopoietic stem cells after allogeneic bone marrow transplantation. , 1994, Blood.

[15]  M. C. Hu,et al.  Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor MpI , 1994, Cell.

[16]  William Vainchenker,et al.  c-Mpl ligand is a humoral regulator of megakaryocytopoiesis , 1994, Nature.

[17]  Scott R. Presnell,et al.  Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo , 1994, Nature.

[18]  D. Goeddel,et al.  Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand , 1994, Nature.

[19]  H. Lu,et al.  Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. , 1994, Cell.

[20]  O. Majdic,et al.  Monocytes do not make mast cells when cultured in the presence of SCF. Characterization of the circulating mast cell progenitor as a c-kit+, CD34+, Ly-, CD14-, CD17-, colony-forming cell. , 1993, Journal of immunology.

[21]  W. Vainchenker,et al.  Oligodeoxynucleotides antisense to the proto-oncogene c-mpl specifically inhibit in vitro megakaryocytopoiesis. , 1993, Blood.

[22]  M. Takagi,et al.  Possible role of stem cell factor as a serum factor: monoclonal anti-c-kit antibody abrogates interleukin-6-dependent colony growth in serum-containing culture. , 1993, Experimental Hematology.

[23]  K. Zsebo,et al.  Development of human mast cells from umbilical cord blood cells by recombinant human and murine c-kit ligand. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M. Heinrich,et al.  Constitutive expression of steel factor gene by human stromal cells. , 1993, Blood.

[25]  G. Nilsson,et al.  Recombinant human stem cell factor stimulates differentiation of mast cells from dispersed human fetal liver cells. , 1992, Blood.

[26]  K. Zsebo,et al.  Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture. , 1992, Blood.

[27]  S. Emerson,et al.  Bone marrow stromal fibroblasts secrete interleukin-6 and granulocyte-macrophage colony-stimulating factor in the absence of inflammatory stimulation: demonstration by serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction. , 1992, Blood.

[28]  S. Eto,et al.  Interactions between recombinant human erythropoietin and serum factor(s) on murine megakaryocyte colony formation. , 1992, Blood.

[29]  L. Ashman,et al.  Expression of the YB5.B8 antigen (c-kit proto-oncogene product) in normal human bone marrow. , 1991, Blood.

[30]  D. Metcalfe,et al.  Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells. , 1991, Journal of immunology.

[31]  T. Mosmann,et al.  Interleukin 10: a novel stimulatory factor for mast cells and their progenitors , 1991, The Journal of experimental medicine.

[32]  C. Uyttenhove,et al.  Mast cell growth‐enhancing activity (MEA) is structurally related and functionally identical to the novel mouse T cell growth factor P40/TCGFIII (interleukin 9) , 1990, European journal of immunology.

[33]  A. Dvorak,et al.  Development of human mast cells in vitro. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[34]  A. Dvorak,et al.  Ultrastructure of eosinophils and basophils stimulated to develop in human cord blood mononuclear cell cultures containing recombinant human interleukin-5 or interleukin-3. , 1989, Laboratory investigation; a journal of technical methods and pathology.

[35]  L. Ashman,et al.  Mast cell typing: demonstration of a distinct hematopoietic cell type and evidence for immunophenotypic relationship to mononuclear phagocytes. , 1989, Blood.

[36]  Y. Kitamura,et al.  Heterogeneity of mast cells and phenotypic change between subpopulations. , 1989, Annual review of immunology.

[37]  A. Donnenberg,et al.  Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Church.  Mast cell heterogeneity. , 1988, Progress in clinical and biological research.

[39]  T. Honjo,et al.  Interleukin 4 as an essential factor for in vitro clonal growth of murine connective tissue-type mast cells , 1987, The Journal of experimental medicine.

[40]  T. Suda,et al.  Single-cell origin of mouse hemopoietic colonies expressing multiple lineages in variable combinations. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[41]  J. Ihle,et al.  Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity. , 1983, Journal of immunology.

[42]  W. Sterry,et al.  In vitro generation of mast cell-like cells from human peripheral mononuclear phagocytes. , 1983, International archives of allergy and applied immunology.

[43]  J. Peters,et al.  Spleen colony-forming cell as common precursor of tissue mast cells and granulocytes , 1981, Nature.

[44]  D. Zucker‐Franklin,et al.  Ultrastructural evidence for the common origin of human mast cells and basophils. , 1980, Blood.