Interleukin-6 Directly Modulates Stem Cell Factor-Dependent Development of Human Mast Cells Derived From CD34+Cord Blood Cells

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 496-508 ◽  
Author(s):  
Tatsuya Kinoshita ◽  
Nobukuni Sawai ◽  
Eiko Hidaka ◽  
Tetsuji Yamashita ◽  
Kenichi Koike
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Cord Blood ◽  
Interleukin 6 ◽  
Blood Cells ◽  
Stem Cell Factor ◽  
Flow Cytometric Analysis ◽  
Flow Cytometric ◽  
Cord Blood Cells

In the present study, we attempted to clarify the effects of interleukin-6 (IL-6) on the growth and properties of human mast cells using cultured mast cells selectively generated by stem cell factor (SCF) from CD34+ cord blood cells. The addition of IL-6 to cultures containing mast cells resulted in a substantial reduction of the number of progenies grown by SCF in the liquid culture. This IL-6–mediated inhibition of mast cell growth may be due in part to the suppression at the precursor level, according to the results of a clonal cell culture assay. Moreover, a flow cytometric analysis showed that the cultured mast cells grown in the presence of SCF+IL-6 had decreased c-kit expression. The exposure of cultured mast cells to SCF+IL-6 also caused substantial increases in the cell size, frequency of chymase-positive cells, and intracellular histamine level compared with the values obtained with SCF alone. The flow cytometric analysis showed low but significant levels of expression of IL-6 receptor (IL-6R) and gp130 on the cultured mast cells grown with SCF. The addition of either anti–IL-6R antibody or anti-gp130 antibody abrogated the biological functions of IL-6. Although IL-4 exerted an effect similar to that of IL-6 on the cultured mast cells under stimulation with SCF, the results of comparative experiments suggest that the two cytokines use different regulatory mechanisms. Taken together, the present findings suggest that IL-6 modulates SCF-dependent human mast cell development directly via an IL-6R-gp130 system.

Interleukin-6 Directly Modulates Stem Cell Factor-Dependent Development of Human Mast Cells Derived From CD34+Cord Blood Cells

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 496-508 ◽  
Author(s):  
Tatsuya Kinoshita ◽  
Nobukuni Sawai ◽  
Eiko Hidaka ◽  
Tetsuji Yamashita ◽  
Kenichi Koike
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Cord Blood ◽  
Interleukin 6 ◽  
Blood Cells ◽  
Stem Cell Factor ◽  
Flow Cytometric Analysis ◽  
Flow Cytometric ◽  
Cord Blood Cells

Abstract In the present study, we attempted to clarify the effects of interleukin-6 (IL-6) on the growth and properties of human mast cells using cultured mast cells selectively generated by stem cell factor (SCF) from CD34+ cord blood cells. The addition of IL-6 to cultures containing mast cells resulted in a substantial reduction of the number of progenies grown by SCF in the liquid culture. This IL-6–mediated inhibition of mast cell growth may be due in part to the suppression at the precursor level, according to the results of a clonal cell culture assay. Moreover, a flow cytometric analysis showed that the cultured mast cells grown in the presence of SCF+IL-6 had decreased c-kit expression. The exposure of cultured mast cells to SCF+IL-6 also caused substantial increases in the cell size, frequency of chymase-positive cells, and intracellular histamine level compared with the values obtained with SCF alone. The flow cytometric analysis showed low but significant levels of expression of IL-6 receptor (IL-6R) and gp130 on the cultured mast cells grown with SCF. The addition of either anti–IL-6R antibody or anti-gp130 antibody abrogated the biological functions of IL-6. Although IL-4 exerted an effect similar to that of IL-6 on the cultured mast cells under stimulation with SCF, the results of comparative experiments suggest that the two cytokines use different regulatory mechanisms. Taken together, the present findings suggest that IL-6 modulates SCF-dependent human mast cell development directly via an IL-6R-gp130 system.

The generation of colony-forming cells (CFC) and the expansion of hematopoiesis in cultures of human cord blood cells is dependent on the presence of stem cell factor (SCF)

1993 ◽  
Vol 11 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Anna Rita Migliaccio ◽  
Giovanni Migliaccio ◽  
Brigitte Durand ◽  
GianCarlo Mancini ◽  
John W. Adamson
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Blood Cells ◽  
Stem Cell Factor ◽  
Human Cord Blood ◽  
Cord Blood Cells

Thrombopoietin Augments Stem Cell Factor–Dependent Growth of Human Mast Cells From Bone Marrow Multipotential Hematopoietic Progenitors

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3703-3712 ◽  
Author(s):  
Nobukuni Sawai ◽  
Kenichi Koike ◽  
Hadija Hemed Mwamtemi ◽  
Tatsuya Kinoshita ◽  
Yumi Kurokawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Early Stage ◽  
Flow Cytometric Analysis ◽  
Immunocytochemical Staining ◽  
Cell Lineages ◽  
Human Mast Cells

Abstract 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.

scholarly journals Long-term generation of human mast cells in serum-free cultures of CD34+ cord blood cells stimulated with stem cell factor and interleukin- 3

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3667-3674 ◽  
Author(s):  
B Durand ◽  
G Migliaccio ◽  
NS Yee ◽  
K Eddleman ◽  
T Huima-Byron ◽  
...  
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Growth Factors ◽  
Mast Cells ◽  
Cord Blood ◽  
Stem Cell Factor ◽  
Human Mast Cells ◽  
Differentiated Cells ◽  
Murine Fibroblasts

The generation of murine mast cells is supported by several cytokines, and mast cell lines are frequently established in long-term cultures of normal murine marrow cells. In contrast, growth of human mast cells was initially dependent on coculture with murine fibroblasts. The growth factor produced by murine fibroblasts and required to observe differentiation of human mast cells is attributable in part to stem cell factor (SCF). However, other factors are likely involved. We have previously shown that the combination of SCF and interleukin-3 (IL-3) efficiently sustains proliferation and differentiation of colony- forming cells (CFCs) from pre-CFC enriched from human umbilical cord blood by CD34+ selection. With periodic medium changes and the addition of fresh growth factors, five consecutive cultures of different cord blood samples gave rise to differentiated cells and CFCs for more than 2 months. Although differentiated cells continued to be generated for more than 5 months, CFCs were no longer detectable by day 50 of culture. The cells have the morphology of immature mast cells, are Toluidine blue positive, are karyotypically normal, are CD33+, CD34-, CD45+, c-kit-, and c-fms-, and die in the absence of either SCF or IL- 3. These cells do not form colonies in semisolid culture and are propagated in liquid culture stimulated with SCF and IL-3 at a seeding concentration of no less than 10(4) cells/mL. At refeedings, the cultures contain a high number (= 50%) of dead cells and have a doubling time ranging from 5 to 12 days. This suggests that subsets of the cell population die because of a requirement for a growth factor other than SCF or IL-3. These results indicate that the combination of cord blood progenitor and stem cells, plus a cocktail of growth factors including SCF and IL-3, is capable with high efficiency of giving rise in serum-deprived culture to human mast cells that behave like factor- dependent cell lines. These cells may represent a useful tool for studies of human mast cell differentiation and leukemia.

Non-IgE–dependent activation of human lung– and cord blood–derived mast cells is induced by eosinophil major basic protein and modulated by the membrane form of stem cell factor

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1898-1904 ◽  
Author(s):  
Adrian M. Piliponsky ◽  
Gerald J. Gleich ◽  
Arnon Nagler ◽  
Ilan Bar ◽  
Francesca Levi-Schaffer
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Cord Blood ◽  
Stem Cell Factor ◽  
Basic Protein ◽  
Human Lung ◽  
Late Phase ◽  
Major Basic Protein ◽  
Eosinophil Major Basic Protein

The allergic reaction begins with the antigen-induced aggregation of occupied high-affinity IgE receptors expressed on mast cell surface, their activation, and the release of proinflammatory mediators that cause the “early phase” of this process. In addition, mast cell activation induces the onset of a “late phase” reaction characterized by the tissue infiltration of inflammatory cells, mainly eosinophils. We have hypothesized that during the late phase mast cells interact with and are activated by eosinophils. Here we report that highly purified human lung mast cells became responsive to eosinophil major basic protein (MBP) when in coculture with human lung fibroblasts. In addition, cord blood–derived mast cells maintained in coculture with 3T3 fibroblasts released more histamine and prostaglandin D2 (PGD2) compared with cells maintained in suspension. The fibroblast-derived membrane form of stem cell factor (SCF) was found to be involved in the mast cell increased responsiveness to MBP. In fact, cord blood–derived mast cells cocultured with 3T3 in the presence of antisense for SCF or cocultured with fibroblasts that do not express the membrane form of SCF were inhibited in their histamine-releasing activity toward MBP. In addition, this form of SCF induced the expression of a pertussis toxin–sensitive Gi protein, Gi3 that interacts with MBP to trigger mast cell non-IgE–dependent activation in a manner similar to other cationic compounds such as compound 48/80. Mast cell responsiveness to eosinophil mediators is a potentially novel evidence for an alternative pathway of allergen-independent activation able to contribute to the perpetuation of allergy.

Thrombopoietin Augments Stem Cell Factor–Dependent Growth of Human Mast Cells From Bone Marrow Multipotential Hematopoietic Progenitors

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3703-3712
Author(s):  
Nobukuni Sawai ◽  
Kenichi Koike ◽  
Hadija Hemed Mwamtemi ◽  
Tatsuya Kinoshita ◽  
Yumi Kurokawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Early Stage ◽  
Flow Cytometric Analysis ◽  
Immunocytochemical Staining ◽  
Cell Lineages ◽  
Human Mast Cells

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.

scholarly journals Ultrastructural Studies of Human Basophils and Mast Cells

2005 ◽  
Vol 53 (9) ◽  
pp. 1043-1070 ◽  
Author(s):  
Ann M. Dvorak
Keyword(s):  
Growth Factor ◽  
Mast Cells ◽  
Cord Blood ◽  
Blood Cells ◽  
De Novo ◽  
Ultrastructural Studies ◽  
Specific Growth Factor ◽  
Cord Blood Cells ◽  
Human Basophils

Ultrastructural studies of human mast cells (HMCs) and basophils (HBs) are reviewed. Sources of HMCs include biopsies of tissue sites and in situ study of excised diseased organs; isolated, partially purified samples from excised organs; and growth-factor-stimulated mast cells that develop de novo in cultures of cord blood cells. Sources of HBs for study include partially purified peripheral blood basophils, basophils in tissue biopsies, and specific growth factor-stimulated basophils arising de novo from cord blood cells. The ultrastructural studies reviewed deal with identity, secretion, vesicles, recovery, and synthesis issues related to the biology of these similar cells.

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