5426098 Increase in hematopoietic progenitor cells in peripheral blood by transforming growth factor beta

1996 ◽  
Vol 5 (2) ◽  
pp. V
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Transforming Growth Factor Beta ◽  
Peripheral Blood ◽  
Transforming Growth Factor ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Growth Factor Beta

scholarly journals Interferon-gamma enhances factor-dependent myeloid proliferation of human CD34+ hematopoietic progenitor cells

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2628-2635 ◽  
Author(s):  
C Caux ◽  
I Moreau ◽  
S Saeland ◽  
J Banchereau
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Interferon Gamma ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Bone Marrow Cells ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Ifn Gamma ◽  
Gm Csf

Abstract Numerous studies have shown that interferon-gamma (IFN gamma) inhibits the proliferative effects of colony-stimulating factors (CSFs) on human bone marrow cells. In the present study we investigated the effects of IFN gamma and other described inhibitory factors on the proliferation of highly purified CD34+ human hematopoietic progenitor cells (HPC) in response to recombinant CSFs. While transforming growth factor-beta (TGF beta) and IFN alpha were highly inhibitory, IFN gamma strongly potentiated interleukin-3 (IL-3) and, to a lesser extent, granulocyte- macrophage-CSF (GM-CSF) induced growth of CD34+ HPC. IFN gamma had no significant proliferative effect per se, and did not affect granulocyte- CSF (G-CSF)-dependent cell proliferation. Within 10 days the number of viable cells generated in the presence of IL-3 + IFN gamma was two times higher than in the presence of IL-3 alone. Limiting dilution analysis showed that IFN gamma acts directly on its target cell to increase the frequency of IL-3-responding cells without affecting the average size of the IL-3-dependent clones. Enhanced frequency of IL-3- and GM-CSF-responding cells was also observed in colony assays where the addition of IFN gamma increased by twofold to threefold the number of granulocyte colony-forming units (CFU-G), macrophage CFUs (CFU-M), granulocyte-macrophage CFUs (CFU-GM), and mixed erythroid (E-MIX). In contrast, IFN gamma did not affect the generation of erythroid burst- forming units (BFU-e) in such cultures. In longer-term culture, the combination of IFN gamma and IL-3 did not alter the lineage distribution of the cells when compared with IL-3 alone. However, after 15 days, when mature cells were present in the cultures, IFN gamma displayed cell concentration-related growth-inhibitory effects. Thus, IFN gamma appears to stimulate the early stage of myelopoiesis by enhancing the frequency of growth factor-responding cells but, unlike tumor necrosis factor alpha (TNF alpha), does not alter cell differentiation.

scholarly journals Interferon-gamma enhances factor-dependent myeloid proliferation of human CD34+ hematopoietic progenitor cells

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2628-2635 ◽  
Author(s):  
C Caux ◽  
I Moreau ◽  
S Saeland ◽  
J Banchereau
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Interferon Gamma ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Bone Marrow Cells ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Ifn Gamma ◽  
Gm Csf

Numerous studies have shown that interferon-gamma (IFN gamma) inhibits the proliferative effects of colony-stimulating factors (CSFs) on human bone marrow cells. In the present study we investigated the effects of IFN gamma and other described inhibitory factors on the proliferation of highly purified CD34+ human hematopoietic progenitor cells (HPC) in response to recombinant CSFs. While transforming growth factor-beta (TGF beta) and IFN alpha were highly inhibitory, IFN gamma strongly potentiated interleukin-3 (IL-3) and, to a lesser extent, granulocyte- macrophage-CSF (GM-CSF) induced growth of CD34+ HPC. IFN gamma had no significant proliferative effect per se, and did not affect granulocyte- CSF (G-CSF)-dependent cell proliferation. Within 10 days the number of viable cells generated in the presence of IL-3 + IFN gamma was two times higher than in the presence of IL-3 alone. Limiting dilution analysis showed that IFN gamma acts directly on its target cell to increase the frequency of IL-3-responding cells without affecting the average size of the IL-3-dependent clones. Enhanced frequency of IL-3- and GM-CSF-responding cells was also observed in colony assays where the addition of IFN gamma increased by twofold to threefold the number of granulocyte colony-forming units (CFU-G), macrophage CFUs (CFU-M), granulocyte-macrophage CFUs (CFU-GM), and mixed erythroid (E-MIX). In contrast, IFN gamma did not affect the generation of erythroid burst- forming units (BFU-e) in such cultures. In longer-term culture, the combination of IFN gamma and IL-3 did not alter the lineage distribution of the cells when compared with IL-3 alone. However, after 15 days, when mature cells were present in the cultures, IFN gamma displayed cell concentration-related growth-inhibitory effects. Thus, IFN gamma appears to stimulate the early stage of myelopoiesis by enhancing the frequency of growth factor-responding cells but, unlike tumor necrosis factor alpha (TNF alpha), does not alter cell differentiation.

scholarly journals Bidirectional effects of transforming growth factor beta (TGF-beta) on colony-stimulating factor-induced human myelopoiesis in vitro: differential effects of distinct TGF-beta isoforms

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2239-2247 ◽  
Author(s):  
SE Jacobsen ◽  
JR Keller ◽  
FW Ruscetti ◽  
P Kondaiah ◽  
AB Roberts ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hematopoietic Progenitor Cells ◽  
Colony Stimulating Factor ◽  
Tgf Beta ◽  
Hematopoietic Progenitor ◽  
Growth Factor Beta ◽  
Beta 2 ◽  
Macrophage Colony ◽  
Stimulating Factor

Transforming growth factor-beta (TGF-beta) has potent antiproliferative effects on human hematopoietic progenitor cells. We report here that TGF-beta 1 and -beta 2 also exert bimodal dose-dependent stimulation of granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte- CSF-induced day 7 granulocyte-macrophage colony-forming units. This increase in colony formation was restricted to low doses (0.01 to 1.0 ng/mL) of TGF-beta 1 and was due to increased granulopoiesis, showing that TGF-beta can affect the differentiation as well as the proliferation of hematopoietic progenitors. Furthermore, TGF-beta 3 was found to be a more potent inhibitor of hematopoietic progenitor cells than TGF-beta 1 and -beta 2. In contrast to the bidirectional proliferative effects of TGF-beta 1 and -beta 2, the effects of TGF- beta 3 on human hematopoiesis were only inhibitory, showing for the first time that TGF-beta isoforms differ not only in potencies but also with regard to the nature of the response they elicit.

scholarly journals Inhibition of purified CD34+ hematopoietic progenitor cells by human immunodeficiency virus 1 or gp120 mediated by endogenous transforming growth factor beta 1.

1996 ◽  
Vol 183 (1) ◽  
pp. 99-108 ◽  
Author(s):  
G Zauli ◽  
M Vitale ◽  
D Gibellini ◽  
S Capitani
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Transforming Growth Factor ◽  
Hematopoietic Progenitor Cells ◽  
Tgf Beta ◽  
Hematopoietic Progenitor ◽  
Cd34 Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

Human CD34+ hematopoietic progenitor cells, stringently purified from the peripheral blood of 20 normal donors, showed an impaired survival and clonogenic capacity after exposure to either heat-inactivated human immunodeficiency virus (HIV) 1 (strain IIIB) or cross-linked envelope gp120. Cell cycle analysis, performed at different times in serum-free liquid culture, showed an accumulation in G0/G1 in HIV-1- or gp120-treated cells and a progressive increase of cells with subdiploid DNA content, characteristic of apoptosis. In blocking experiments with anti-transforming growth factor (TGF) beta 1 neutralizing serum or TGF-beta 1 oligonucleotides, we demonstrated that the HIV-1- or gp120-mediated suppression of CD34+ cell growth was almost entirely due to an upregulation of endogenous TGF-beta 1 produced by purified hematopoietic progenitors. Moreover, by using a sensitive assay on the CCL64 cell line, increased levels of bioactive TGF-beta 1 were recovered in the culture supernatant of HIV-1/gp120-treated CD34+ cells. Anti-TGF-beta 1 neutralizing serum or TGF-beta 1 oligonucleotides were also effective in inducing a significant increase of the plating efficiency of CD34+ cells, purified from the peripheral blood of three HIV-1-seropositive individuals, suggesting that a similar mechanism may be also operative in vivo. The relevance of these findings to a better understanding of the pathogenesis of HIV-1-related cytopenias is discussed.

Transforming Growth Factor-β1 Polarizes Murine Hematopoietic Progenitor Cells to Generate Langerhans Cell-Like Dendritic Cells Through a Monocyte/Macrophage Differentiation Pathway

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1208-1220 ◽  
Author(s):  
Yi Zhang ◽  
Yan-yun Zhang ◽  
Masafumi Ogata ◽  
Pan Chen ◽  
Akihisa Harada ◽  
...  
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Macrophage Differentiation ◽  
Gm Csf ◽  
Tgf Β1 ◽  
E Cadherin

We have recently demonstrated that CD11b−/dullCD11c+ and CD11b+hiCD11c+ dendritic cell (DC) precursor subsets represent two distinct DC differentiation pathways from murine bone marrow lineage-phenotype negative (Lin−)c-kit+ hematopoietic progenitor cells (HPCs) stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) + stem cell factor (SCF) + tumor necrosis factor  (TNF). We show here that transforming growth factor-β1 (TGF-β1) significantly inhibits the generation of these CD11b−/dullCD11c+ and CD11b+hiCD11c+ DC precursors. Phenotypically, this inhibitory effect was accompanied by markedly suppressed expression of Ia and CD86 antigens as well as major histocompatibility complex (MHC) class II transactivator (CIITA) and CC-chemokine receptor 7 (CCR7) mRNAs in Lin−c-kit+ HPC cultures stimulated with GM-CSF + SCF + TNF at day 6. TGF-β1 could also suppress mature DC differentiation from CD11b+hiCD11c+ DC precursors, but not the differentiation from CD11b−/dullCD11c+ DC precursors. In the absence of TNF, TGF-β1 markedly suppressed the expression of CIITA and CCR7 mRNAs in GM-CSF + SCF-stimulated Lin−c-kit+ HPCs at either day 6 or day 12 and induced the differentiation solely into monocytes/macrophages as evident in morphology, active phagocytic, and endocytic activities. These cells expressed high levels of F4/80 and E-cadherin antigens, but low or undetectable levels of Ia, CD86, and CD40 molecules. However, upon the stimulation with TNF + GM-CSF, these cells could further differentiate into mature DCs expressing high levels of Ia and E-cadherin, characteristics for Langerhans cells (LCs), and gained the capacity of enhancing allogenic MLR. Taken together, all of these findings suggest that TGF-β1 polarizes murine HPCs to generate LC-like DCs through a monocyte/macrophage differentiation pathway.

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