The regulation of the development and function of dendritic cell subsets by GM-CSF: More than a hematopoietic growth factor

Hematopoietins, interleukin (IL)-3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) have previously been shown to prolong eosinophil survival and abrogate apoptosis. The objective of this study was to investigate the effect of transforming growth factor beta (TGF-beta) on eosinophil survival and apoptosis. Eosinophils from peripheral blood of mildly eosinophilic donors were isolated to > 97% purity using discontinuous Percoll density gradient. Eosinophils were cultured with hematopoietins with or without TGF-beta for 4 d and their viability was assessed. We confirmed previous observations that hematopoietins prolonged eosinophil survival and inhibited apoptosis. TGF-beta at concentrations > or = 10(-12) M abrogated the survival-prolonging effects of hematopoietins in a dose-dependent manner and induced apoptosis as determined by DNA fragmentation in agarose gels. The effect of TGF-beta was blocked by an anti-TGF-beta antibody. The anti-TGF-beta antibody also prolonged eosinophil survival on its own. The culture of eosinophils with IL-3 and GM-CSF stimulated the synthesis of GM-CSF and IL-5, respectively, suggesting an autocrine mechanism of growth factor production. TGF-beta inhibited the synthesis of GM-CSF and IL-5 by eosinophils. TGF-beta did not have any effect on the expression of GM-CSF receptors on eosinophils. We also studied the effect of TGF-beta on eosinophil function and found that TGF-beta inhibited the release of eosinophil peroxidase. Thus, TGF-beta seems to inhibit eosinophil survival and function. The inhibition of endogenous synthesis of hematopoietins may be one mechanism by which TGF-beta blocks eosinophil survival and induces apoptosis.

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Hematopoietic growth factor (G-CSF or GM-CSF) after salvage chemotherapy in refractory or relapsed adult de novo acute leukemia

Leukemia & Lymphoma ◽

10.3109/10428199609051625 ◽

1996 ◽

Vol 20 (3-4) ◽

pp. 321-326 ◽

Cited By ~ 2

Author(s):

Rodrigo Martino ◽

Salut Brunet ◽

Anna Sureda ◽

Ramon GuÀRdia ◽

Anna AventiÍN ◽

...

Keyword(s):

Growth Factor ◽

Acute Leukemia ◽

De Novo ◽

Salvage Chemotherapy ◽

Hematopoietic Growth Factor ◽

Gm Csf ◽

Factor G

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Dendritic cell subsets in the intestinal lamina propria: Ontogeny and function

European Journal of Immunology ◽

10.1002/eji.201343740 ◽

2013 ◽

Vol 43 (12) ◽

pp. 3098-3107 ◽

Cited By ~ 86

Author(s):

Emma K. Persson ◽

Charlotte L. Scott ◽

Allan McI. Mowat ◽

William W. Agace

Keyword(s):

Dendritic Cell ◽

Lamina Propria ◽

Intestinal Lamina Propria ◽

Dendritic Cell Subsets ◽

And Function

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Human Dendritic Cell Subsets from Spleen and Blood Are Similar in Phenotype and Function but Modified by Donor Health Status

The Journal of Immunology ◽

10.4049/jimmunol.1002632 ◽

2011 ◽

Vol 186 (11) ◽

pp. 6207-6217 ◽

Cited By ~ 154

Author(s):

Diana Mittag ◽

Anna I. Proietto ◽

Thomas Loudovaris ◽

Stuart I. Mannering ◽

David Vremec ◽

...

Keyword(s):

Health Status ◽

Dendritic Cell ◽

Human Dendritic Cell ◽

Dendritic Cell Subsets ◽

And Function

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IL-3 in dendritic cell development and function: a comparison with GM-CSF and IL-4

Immunobiology ◽

10.1016/j.imbio.2004.03.001 ◽

2004 ◽

Vol 209 (1-2) ◽

pp. 79-87 ◽

Cited By ~ 31

Author(s):

Manfred B. Lutz

Keyword(s):

Dendritic Cell ◽

Cell Development ◽

Gm Csf ◽

And Function

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Stimulation of neutrophil production in CSF-1-responsive clones

Blood ◽

10.1182/blood.v72.3.898.bloodjournal723898 ◽

1988 ◽

Vol 72 (3) ◽

pp. 898-902 ◽

Cited By ~ 8

Author(s):

G Rothstein ◽

SM Rhondeau ◽

CA Peters ◽

RD Christensen ◽

D Lynch ◽

...

Keyword(s):

Growth Factor ◽

Hematopoietic Growth Factor ◽

Gm Csf ◽

Low Concentrations ◽

Stimulation Of

The hematopoietic growth factor CSF-1 has been considered relatively lineage specific for the production of macrophages, whereas GM-CSF elicits a predominance of neutrophils. It is likely that in vivo, individual clones are stimulated by the two CSFs, although the effect of dual stimulation on progenitors and their progeny has not been completely explored. We found that in cultures initiated with low concentrations of CSF-1 or GM-CSF, alone or in combination, production of macrophages predominated. Maximally stimulatory concentrations of CSF-1 elicited a predominance of macrophages, whereas maximal GM-CSF elicited many more neutrophil/macrophage colonies and pure neutrophil colonies. A combination of maximal CSF-1 and GM-CSF elicited the same differentiation as GM-CSF alone. Delayed addition of GM-CSF to cultures initiated with CSF-1 elicited colonies indistinguishable from GM-CSF alone, suggesting that neutrophil production had been switched on by GM- CSF. In mapping studies, colonies initiated by CSF-1 increased or switched on neutrophil production when GM-CSF was added as a second stimulus. These studies show that individual clones are responsive to both CSFs, and that the differentiating influence of GM-CSF predominates over that of CSF-1. In cultures to which only CSF-1 was added, a population of progenitors was sustained that produced neutrophils only after a GM-CSF stimulus. Thus, CSF-1 may participate in maintaining a reserve of progenitors for neutrophils during periods of increased neutrophil demand.

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Toll-like receptor expression and function in human dendritic cell subsets: implications for dendritic cell-based anti-cancer immunotherapy

Cancer Immunology Immunotherapy ◽

10.1007/s00262-010-0833-1 ◽

2010 ◽

Vol 59 (10) ◽

pp. 1573-1582 ◽

Cited By ~ 167

Author(s):

Gerty Schreibelt ◽

Jurjen Tel ◽

Kwinten H. E. W. J. Sliepen ◽

Daniel Benitez-Ribas ◽

Carl G. Figdor ◽

...

Keyword(s):

Dendritic Cell ◽

Cancer Immunotherapy ◽

Receptor Expression ◽

Human Dendritic Cell ◽

Toll Like Receptor ◽

Anti Cancer ◽

Dendritic Cell Subsets ◽

And Function

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Effect of mast cell growth factor (c-kit ligand) on clonogenic leukemic precursor cells

Blood ◽

10.1182/blood.v80.3.750.750 ◽

1992 ◽

Vol 80 (3) ◽

pp. 750-757 ◽

Cited By ~ 28

Author(s):

HM Goselink ◽

DE Williams ◽

WE Fibbe ◽

HW Wessels ◽

GC Beverstock ◽

...

Keyword(s):

Bone Marrow ◽

Growth Factor ◽

Colony Formation ◽

Myeloid Leukemia ◽

Chronic Phase ◽

Precursor Cells ◽

Hematopoietic Growth Factor ◽

Gm Csf ◽

Acute Myeloid ◽

Mast Cell Growth Factor

Abstract Mast cell growth factor (MGF), the ligand for the c-kit receptor, has been shown to be a hematopoietic growth factor that preferentially stimulates the proliferation of immature hematopoietic progenitor cells (HPC). We studied the effect of MGF on the in vitro growth of clonogenic leukemic precursor cells in the presence or absence of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or erythropoietin (EPO). Leukemic blood and bone marrow cells from patients with various types of acute myeloid leukemia (AML), chronic myeloid leukemia (CML) in chronic phase, as well as bone marrow samples from patients with myelodysplastic syndromes (MDS) were studied. MGF as a single factor did not induce significant colony formation by clonogenic leukemic precursor cells. In the presence of IL- 3 and/or GM-CSF, MGF weakly stimulated the colony formation by clonogenic precursor cells from patients with AML. In contrast, in the presence of IL-3 and/or GM-CSF, MGF strongly induced both size and number of leukemic colonies from patients with CML in chronic phase. Furthermore, in the presence of EPO, MGF strongly stimulated erythroid colony formation by CML precursor cells. Cytogenetic analysis of the colonies showed that all metaphases after 1 week of culture were derived from the leukemic clone. In patients with MDS, MGF strongly stimulated myeloid colony formation in the presence of IL-3 and/or GM- CSF (up to fourfold), and erythroid colony formation in the presence of EPO (up to eightfold). Not only the number, but also the size of the colonies increased. In the presence of MGF, the percentage of normal metaphases increased in three patients tested after 1 week of culture compared with the initial suspension, suggesting that the normal HPC were preferentially stimulated compared with the preleukemic precursor cells. In the absence of exogenous EPO and in the presence of 10% human AB serum, MGF in the presence of IL-3 and/or GM-CSF induced erythroid colony formation from normal bone marrow and patients with MDS or CML, illustrating that MGF greatly diminished the EPO requirement for erythroid differentiation. These results indicate that MGF may be a candidate as a hematopoietic growth factor to stimulate normal hematopoiesis in patients with acute myeloid leukemia, or with myelodysplastic syndromes.

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