Characterization of factor-independent variants derived from TF-1 hematopoietic progenitor cells: the role of the Raf/MAP kinase pathway in the anti-apoptotic effect of GM-CSF

The recently cloned interleukin 13 (IL-13) shares most investigated biological activities on B lymphocytes and monocytes with IL-4. In this study we investigated for the first time the potential role of IL-13 in the regulation of the growth of hematopoietic progenitor cells. IL-13 enhanced stem cell factor (SCF)-induced proliferation of Lin-Sca-1+ bone marrow progenitor cells more potently than IL-4. The effect of IL-13 was purely synergistic, since IL-13 alone stimulated no colony formation. Single cell experiments suggested that the synergistic effect of IL-13 on Lin-Sca-1+ progenitors was directly mediated. In contrast, IL-13 had no synergistic activity on SCF-induced proliferation of the more mature Lin-Sca-1- progenitor cells. Thus, the cloning frequency in response to SCF + IL-13 was at least 20-fold higher in the Lin-Sca-1+ than the Lin-Sca-1- progenitor cell population. Furthermore, IL-13 but not IL-4 synergistically enhanced colony formation of Lin-Sca-1+ progenitors in response to granulocyte/macrophage colony-stimulating factor (GM-CSF) (threefold), whereas both IL-4 and IL-13 enhanced G-CSF-induced colony formation (threefold), and neither of the two significantly affected CSF-1 and IL-3-induced proliferation. Finally, whereas stimulation of Lin-Sca-1+ progenitors by SCF + G-CSF resulted in the formation of 90% granulocytes, the addition of IL-13 resulted in the production of macrophages exclusively. This novel effect on differentiation was directly mediated, shared with IL-4, and could not be observed on Lin-Sca-1- progenitor cells. Collectively, these findings indicate a novel role of IL-13 in early myelopoiesis, partially overlapping but also different from that of IL-4.

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Congenital Pulmonary Alveolar Proteinosis iPS-derived hematopoietic progenitor cells (HPCs) reveal functional defects upon GM-CSF administration

Pneumologie ◽

10.1055/s-0034-1376847 ◽

2014 ◽

Vol 68 (06) ◽

Author(s):

A Mucci ◽

N Lachmann ◽

C Happle ◽

M Ackermann ◽

S Glage ◽

...

Keyword(s):

Progenitor Cells ◽

Pulmonary Alveolar Proteinosis ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Gm Csf ◽

Alveolar Proteinosis ◽

Functional Defects

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Characterization of CD34+ hematopoietic progenitor cells in JAK2 V617F and CALR -mutated myeloproliferative neoplasms

Leukemia Research ◽

10.1016/j.leukres.2016.06.009 ◽

2016 ◽

Vol 48 ◽

pp. 11-15 ◽

Cited By ~ 6

Author(s):

Anna Angona ◽

Alberto Alvarez-Larrán ◽

Beatriz Bellosillo ◽

Raquel Longarón ◽

Laura Camacho ◽

...

Keyword(s):

Progenitor Cells ◽

Myeloproliferative Neoplasms ◽

Jak2 V617f ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor

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Role of HIV-1 in the Functional Impairment of CD34+ Hematopoietic Progenitor Cells

Molecular Biology of Hematopoiesis 5 ◽

10.1007/978-1-4613-0391-6_37 ◽

1996 ◽

pp. 307-312

Author(s):

Giorgio Zauli

Keyword(s):

Progenitor Cells ◽

Functional Impairment ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Hiv 1

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Murine yolk sac endoderm- and mesoderm-derived cell lines support in vitro growth and differentiation of hematopoietic cells

Blood ◽

10.1182/blood.v83.9.2436.2436 ◽

1994 ◽

Vol 83 (9) ◽

pp. 2436-2443 ◽

Cited By ~ 49

Author(s):

MC Yoder ◽

VE Papaioannou ◽

PP Breitfeld ◽

DA Williams

Keyword(s):

Progenitor Cells ◽

Cell Lines ◽

Stromal Cell ◽

Hematopoietic Cells ◽

Yolk Sac ◽

Hematopoietic Progenitor Cells ◽

Visceral Endoderm ◽

Hematopoietic Progenitor

Abstract The mechanisms involved in the induction of yolk sac mesoderm into blood islands and the role of visceral endoderm and mesoderm cells in regulating the restricted differentiation and proliferation of hematopoietic cells in the yolk sac remain largely unexplored. To better define the role of murine yolk sac microenvironment cells in supporting hematopoiesis, we established cell lines from day-9.5 gestation murine yolk sac visceral endoderm and mesoderm layers using a recombinant retrovirus vector containing Simian virus 40 large T- antigen cDNA. Obtained immortalized cell lines expressed morphologic and biosynthetic features characteristic of endoderm and mesoderm cells from freshly isolated yolk sacs. Similar to the differentiation of blood island hematopoietic cells in situ, differentiation of hematopoietic progenitor cells in vitro into neutrophils was restricted and macrophage production increased when bone marrow (BM) progenitor cells were cultured in direct contact with immortalized yolk sac cell lines as compared with culture on adult BM stromal cell lines. Yolk sac- derived cell lines also significantly stimulated the proliferation of hematopoietic progenitor cells compared with the adult BM stromal cell lines. Thus, yolk sac endoderm- and mesoderm-derived cells, expressing many features of normal yolk sac cells, alter the growth and differentiation of hematopoietic progenitor cells. These cells will prove useful in examining the cellular interactions between yolk sac endoderm and mesoderm involved in early hematopoietic stem cell proliferation and differentiation.

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Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic/Langerhans cells from cord blood CD34+ hematopoietic progenitor cells

Blood ◽

10.1182/blood.v87.6.2376.bloodjournal8762376 ◽

1996 ◽

Vol 87 (6) ◽

pp. 2376-2385 ◽

Cited By ~ 85

Author(s):

C Caux ◽

B Vanbervliet ◽

C Massacrier ◽

I Durand ◽

J Banchereau

Keyword(s):

Tumor Necrosis Factor ◽

Cord Blood ◽

Progenitor Cells ◽

Langerhans Cells ◽

Tumor Necrosis ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Gm Csf ◽

Cord Blood Cd34 ◽

Necrosis Factor

We have previously shown that tumor necrosis factor (TNF)alpha strongly potentiates the granulocyte-macrophage colony-stimulating factor (GM- CSF)/interleukin (IL)-3-dependent proliferation of CD34+ hematopoietic progenitor cells (HPC) through the recruitment of early progenitors with high proliferative potential. Furthermore, the combination of GM- CSF and TNFalpha allows the generation of large numbers of dendritic/Langerhans cells (D-Lc). Herein, we analyzed whether IL-3, when combined to TNFalpha would, as does GM-CSF, allow the generation of CD1a+ D-Lc. Accordingly, cultures of cord blood CD34+ HPC with IL-3 + TNFalpha yielded 20% to 60% CD14+ cells and 11% to 17% CD1a+ cells, while IL-3 alone did not generate significant numbers of CD1a+ cells. Although the percentage of CD1a+ cells detected in IL3 + TNFalpha was lower than that observed in GM-CSF + TNFalpha (42% to 78%), the strong growth induced by IL-3 + TNFalpha generated as many CD1a+ cells as did GM-CSF + TNFalpha. The CD14+ and CD1a+ cells generated with IL-3 + TNFalpha are similar to CD14+ and CD1a+ cells generated in GM-CSF alone and GM-CSF + TNFalpha, respectively. CD1a+ cells differed from CD14+ cells by (1) dendritic morphology, (2) higher expression of CD1a, CD1c, CD4, CD40, adhesion molecules (CD11c, CD54, CD58), major histocompatibility complex (MHC) class II molecules and CD28 ligands (CD80 and CD86), (3) lack of Fc receptor FcgammaRI (CD64) and complement receptor CR1 (CD35) expression, and (4) stronger induction of allogeneic T-cell proliferation. Thus, in combination with TNFalpha, IL-3 is as potent as GM-CSF for the generation of CD1a+ D-Lc from cord blood CD34+ HPC. The dendritic cell inducing ability of IL-3 may explain why mice with inactivated GM-CSF gene display dendritic cells.

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Extracellular Zinc Triggers ERK-dependent Activation of Na+/H+Exchange in Colonocytes Mediated by the Zinc-sensing Receptor

Journal of Biological Chemistry ◽

10.1074/jbc.m406581200 ◽

2004 ◽

Vol 279 (50) ◽

pp. 51804-51816 ◽

Cited By ~ 73

Author(s):

Hagit Azriel-Tamir ◽

Haleli Sharir ◽

Betty Schwartz ◽

Michal Hershfinkel

Keyword(s):

Cell Proliferation ◽

Map Kinase ◽

Ph Homeostasis ◽

Ht29 Cells ◽

Intracellular Release ◽

Map Kinase Pathway ◽

Zinc Sensing ◽

Multiple Signaling ◽

Kinase Pathway

Extracellular zinc promotes cell proliferation and its deficiency leads to impairment of this process, which is particularly important in epithelial cells. We have recently characterized a zinc-sensing receptor (ZnR) linking extracellular zinc to intracellular release of calcium. In the present study, we addressed the role of extracellular zinc, acting via the ZnR, in regulating the MAP kinase pathway and Na+/H+exchange in colonocytes. We demonstrate that Ca2+release, mediated by the ZnR, induces phosphorylation of ERK1/2, which is highly metal-specific, mediated by physiological concentrations of extracellular Zn2+but not by Cd2+, Fe2+, Ni2+, or Mn2+. Desensitization of the ZnR by Zn2+, is followed by ∼90% inhibition of the Zn2+-dependent ERK1/2 phosphorylation, indicating that the ZnR is a principal link between extracellular Zn2+and ERK1/2 activation. Application of both the IP3pathway and PI 3-kinase antagonists largely inhibited Zn2+-dependent ERK1/2 phosphorylation. The physiological significance of the Zn2+-dependent activation of ERK1/2 was addressed by monitoring Na+/H+exchanger activity in HT29 cells and in native colon epithelium. Preincubation of the cells with zinc was followed by robust activation of Na+/H+exchange, which was eliminated by cariporide (0.5 μm); indicating that zinc enhances the activity of NHE1. Activation of NHE1 by zinc was totally blocked by the ERK1/2 inhibitor, U0126. Prolonged acidification, in contrast, stimulates NHE1 by a distinct pathway that is not affected by extracellular Zn2+or inhibitors of the MAP kinase pathway. Desensitization of ZnR activity eliminates the Zn2+-dependent, but not the prolonged acidification-dependent activation of NHE1, indicating that Zn2+-dependent activation of H+extrusion is specifically mediated by the ZnR. Our results support a role for extracellular zinc, acting through the ZnR, in regulating multiple signaling pathways that affect pH homeostasis in colonocytes. Furthermore activation of both, ERK and NHE1, by extracellular zinc may provide the mechanism linking zinc to enhanced cell proliferation.

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A role for calmodulin in the growth of human hematopoietic progenitor cells

Blood ◽

10.1182/blood.v75.7.1446.1446 ◽

1990 ◽

Vol 75 (7) ◽

pp. 1446-1454 ◽

Cited By ~ 11

Author(s):

N Katayama ◽

M Nishikawa ◽

F Komada ◽

N Minami ◽

S Shirakawa

Keyword(s):

Progenitor Cells ◽

Colony Formation ◽

Hematopoietic Progenitor Cells ◽

Dependent Manner ◽

Hematopoietic Progenitor ◽

Erythroid Progenitor ◽

Gm Csf ◽

Erythroid Progenitor Cells ◽

Dependent Inhibition ◽

Dose Dependent

Abstract A possible role for calmodulin in the colony growth of human hematopoietic progenitor cells was investigated using pharmacologic approaches. We obtained evidence for a dose-dependent inhibition of colony formation of myeloid progenitor cells (CFU-C) stimulated by interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte CSF (G-CSF) by three calmodulin antagonists, N- (6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), N- (4-aminobutyl)-5-chloro-2-naphthalenesulfonamide hydrochloride (W-13), and trifluoperazine. Chlorine-deficient analogs of W-7 and W-13, with a lower affinity for calmodulin, did not inhibit the growth of CFU-C colonies. W-7, W-13, and trifluoperazine inhibited the colony formation of immature erythroid progenitor cells (BFU-E) stimulated by IL-3 plus erythropoietin (Ep) or GM-CSF plus Ep, in a dose-dependent manner, while they did not affect the colony formation of mature erythroid progenitor cells (CFU-E) induced by Ep. W-7, W-13, and trifluoperazine also led to a dose-dependent inhibition of GM-CSF-induced colony formation of KG-1 cells. Calmodulin-dependent kinase activity derived from the KG-1 cells was inhibited by these three calmodulin antagonists in a dose-dependent manner. These data suggest that calmodulin may play an important regulatory role via a common process in the growth of hematopoietic progenitor cells stimulated by IL-3, GM-CSF, and G-CSF. Mechanisms related to the growth signal of Ep apparently are not associated with calmodulin-mediated systems.

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