scholarly journals Effects of recombinant GM-CSF on the blast cells of acute myeloblastic leukemia

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 313-316 ◽  
Author(s):  
T Hoang ◽  
N Nara ◽  
G Wong ◽  
S Clark ◽  
MD Minden ◽  
...  
Keyword(s):  
Suspension Culture ◽  
Adherent Cells ◽  
Colony Stimulating Factor ◽  
Response Curves ◽  
Self Renewal ◽  
Gm Csf ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) were compared to those of media conditioned by the continuous bladder carcinoma line, HTB9 (HTB9-CM), using three criteria. First, both GM-CSF and HTB9-CM stimulated blast colony formation in methylcellulose cultures, patient-to-patient variations were seen in the dose-response curves, and GM-CSF was effective, but less so that HTB9-CM. Second, GM-CSF also enhanced growth of blast progenitors in suspension culture, indicating its capacity to support self-renewal. GM-CSF was as effective as HTB9-CM in the production of adherent cells during the growth of blast cells in suspension, a finding that is interpreted to mean that GM-CSF also supports postdeterministic events in blast differentiation. Finally, colonies growing in the presence of GM-CSF were not phenotypically different than those stimulated by HTB9-CM.

scholarly journals Effects of recombinant GM-CSF on the blast cells of acute myeloblastic leukemia

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 313-316 ◽  
Author(s):  
T Hoang ◽  
N Nara ◽  
G Wong ◽  
S Clark ◽  
MD Minden ◽  
...  
Keyword(s):  
Suspension Culture ◽  
Adherent Cells ◽  
Colony Stimulating Factor ◽  
Response Curves ◽  
Self Renewal ◽  
Gm Csf ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) were compared to those of media conditioned by the continuous bladder carcinoma line, HTB9 (HTB9-CM), using three criteria. First, both GM-CSF and HTB9-CM stimulated blast colony formation in methylcellulose cultures, patient-to-patient variations were seen in the dose-response curves, and GM-CSF was effective, but less so that HTB9-CM. Second, GM-CSF also enhanced growth of blast progenitors in suspension culture, indicating its capacity to support self-renewal. GM-CSF was as effective as HTB9-CM in the production of adherent cells during the growth of blast cells in suspension, a finding that is interpreted to mean that GM-CSF also supports postdeterministic events in blast differentiation. Finally, colonies growing in the presence of GM-CSF were not phenotypically different than those stimulated by HTB9-CM.

scholarly journals Differentiation of human dendritic cells from monocytes in vitro using granulocyte-macrophage colony stimulating factor and low concentration of interleukin-4

2003 ◽  
Vol 60 (5) ◽  
pp. 531-538 ◽  
Author(s):  
Miodrag Colic ◽  
Dusan Jandric ◽  
Zorica Stojic-Vukanic ◽  
Jelena Antic-Stankovic ◽  
Petar Popovic ◽  
...  
Keyword(s):  
T Cells ◽  
Interleukin 4 ◽  
Adherent Cells ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Alloreactive T Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Human Dendritic Cells ◽  
Stimulating Factor

Several laboratories have developed culture systems that allow the generation of large numbers of human dendritic cells (DC) from monocytes using granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukin-4 (IL-4). In this work we provided evidence that GM-CSF (100 ng/ml) in combination with a low concentration of IL-4 (5 ng/ml) was efficient in the generation of immature, non-adherent, monocyte-derived DC as the same concentration of GM-CSF, and ten times higher concentration of IL-4 (50 ng/ml). This conclusion was based on the similar phenotype profile of DC such as the expression of CD1a, CD80, CD86, and HLA-DR, down-regulation of CD14, and the absence of CD83, as well as on their similar allostimulatory activity for T cells. A higher number of cells remained adherent in cultures with lower concentrations of IL-4 than in cultures with higher concentrations of the cytokine. However, most of these adherent cells down-regulated CD14 and stimulated the proliferation of alloreactive T cells. In contrast adherent cells cultivated with GM-CSF alone were predominantly macrophages as judged by the expression of CD14 and the inefficiency to stimulate alloreactive T cells. DC generated in the presence of lower concentrations of IL-4 had higher proapoptotic potential for the Jurkat cell line than DC differentiated with higher concentrations of IL-4, suggesting their stronger cytotoxic, anti-tumor effect.

scholarly journals Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 925-929 ◽  
Author(s):  
PD Emanuel ◽  
LJ Bates ◽  
RP Castleberry ◽  
RJ Gualtieri ◽  
KS Zuckerman
Keyword(s):  
Growth Factor ◽  
Dose Response ◽  
Myeloid Leukemia ◽  
Colony Stimulating Factor ◽  
Response Curves ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Dose Response Curves ◽  
Macrophage Colony ◽  
Stimulating Factor

Juvenile chronic myelogenous leukemia (JCML) is a good model for the study of myeloproliferation because JCML hematopoietic progenitor cells grow in vitro at very low cell densities without the addition of exogenous stimulus. Previous studies have demonstrated that this proliferation is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF), and that removal of monocytes from the cell population before culture eliminates this “spontaneous” myeloproliferation, suggesting a paracrine role of monocyte stimulation. However, subsequent studies have shown that increased GM-CSF production from the JCML monocytes is not a consistent finding and therefore not a plausible sole mechanism. In examining hematopoietic growth factor dose- response curves, both JCML GM and erythroid nonadherent progenitor cell populations displayed a marked and selective hypersensitivity to GM- CSF. Responses to interleukin-3 and G-CSF were identical to control dose-response curves. This is the first demonstration of a myeloid leukemia in which hypersensitivity to a specific growth factor appears to be involved in the pathogenesis of the disease.

scholarly journals Proliferation of normal human promyelocytes and myelocytes after a single pulse stimulation by purified GM-CSF or G-CSF

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 640-645
Author(s):  
CG Begley ◽  
NA Nicola ◽  
D Metcalf
Keyword(s):  
Single Pulse ◽  
Colony Stimulating Factor ◽  
Single Exposure ◽  
Gm Csf ◽  
Blast Cells ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Pulse Stimulation

Enriched populations of either normal human promyelocytes and myelocytes or blast cells were obtained by fluorescence-activated cell sorting with the monoclonal antibody WEM-G11. These populations were used to study the effect of pulse stimulation by purified recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) or cross-reacting purified murine granulocyte colony-stimulating factor (G- CSF). Maximal clone formation by promyelocytes and myelocytes was observed in 1-mL agar cultures stimulated continuously with 400 units of either CSF and in cultures of cells that were pulse stimulated by 3,200 units (or greater) of either CSF. Pulse stimulation by 800 units of GM-CSF or G-CSF generated 75% clone formation, and pulse stimulation by 200 units CSF gave 50% clone formation. The majority of clones formed by pulse-stimulated cells were only two cells in size; however, some clones were up to 15 cells in size after a single exposure to CSF. Clone formation was not observed in cultures of blast cell populations after a single pulse stimulation with GM-CSF or G-CSF.

scholarly journals The effects of three recombinant growth factors, IL-3, GM-CSF, and G- CSF, on the blast cells of acute myeloblastic leukemia maintained in short-term suspension culture

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 657-663 ◽  
Author(s):  
J Miyauchi ◽  
CA Kelleher ◽  
YC Yang ◽  
GG Wong ◽  
SC Clark ◽  
...  
Keyword(s):  
Growth Factors ◽  
Acute Myeloblastic Leukemia ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Gm Csf ◽  
Bladder Cell ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The blast stem cells of acute myeloblastic leukemia (AML) respond in cell culture to growth factors by both self-renewal and terminal divisions. Both of these functions have been shown to be stimulated by the recombinant growth factors granulocyte-macrophage colony- stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). In this paper, recombinant gibbon interleukin-3 (IL-3), homologous to human IL-3, was tested on blast cells and compared with the effects of GM-CSF, G-CSF, and medium conditioned by the bladder cell line 5637 (5637-CM). We found that IL-3 was an effective stimulator of blast renewal and terminal divisions. However, great patient-to-patient variation was found. A graphic method of presenting complex comparisons between growth factors is also included.

scholarly journals The effects of three recombinant growth factors, IL-3, GM-CSF, and G- CSF, on the blast cells of acute myeloblastic leukemia maintained in short-term suspension culture

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 657-663 ◽  
Author(s):  
J Miyauchi ◽  
CA Kelleher ◽  
YC Yang ◽  
GG Wong ◽  
SC Clark ◽  
...  
Keyword(s):  
Growth Factors ◽  
Acute Myeloblastic Leukemia ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Gm Csf ◽  
Bladder Cell ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The blast stem cells of acute myeloblastic leukemia (AML) respond in cell culture to growth factors by both self-renewal and terminal divisions. Both of these functions have been shown to be stimulated by the recombinant growth factors granulocyte-macrophage colony- stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). In this paper, recombinant gibbon interleukin-3 (IL-3), homologous to human IL-3, was tested on blast cells and compared with the effects of GM-CSF, G-CSF, and medium conditioned by the bladder cell line 5637 (5637-CM). We found that IL-3 was an effective stimulator of blast renewal and terminal divisions. However, great patient-to-patient variation was found. A graphic method of presenting complex comparisons between growth factors is also included.

scholarly journals Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 925-929 ◽  
Author(s):  
PD Emanuel ◽  
LJ Bates ◽  
RP Castleberry ◽  
RJ Gualtieri ◽  
KS Zuckerman
Keyword(s):  
Growth Factor ◽  
Dose Response ◽  
Myeloid Leukemia ◽  
Colony Stimulating Factor ◽  
Response Curves ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Dose Response Curves ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Juvenile chronic myelogenous leukemia (JCML) is a good model for the study of myeloproliferation because JCML hematopoietic progenitor cells grow in vitro at very low cell densities without the addition of exogenous stimulus. Previous studies have demonstrated that this proliferation is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF), and that removal of monocytes from the cell population before culture eliminates this “spontaneous” myeloproliferation, suggesting a paracrine role of monocyte stimulation. However, subsequent studies have shown that increased GM-CSF production from the JCML monocytes is not a consistent finding and therefore not a plausible sole mechanism. In examining hematopoietic growth factor dose- response curves, both JCML GM and erythroid nonadherent progenitor cell populations displayed a marked and selective hypersensitivity to GM- CSF. Responses to interleukin-3 and G-CSF were identical to control dose-response curves. This is the first demonstration of a myeloid leukemia in which hypersensitivity to a specific growth factor appears to be involved in the pathogenesis of the disease.

scholarly journals Proliferation of normal human promyelocytes and myelocytes after a single pulse stimulation by purified GM-CSF or G-CSF

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 640-645 ◽  
Author(s):  
CG Begley ◽  
NA Nicola ◽  
D Metcalf
Keyword(s):  
Single Pulse ◽  
Colony Stimulating Factor ◽  
Single Exposure ◽  
Gm Csf ◽  
Blast Cells ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Pulse Stimulation

Abstract Enriched populations of either normal human promyelocytes and myelocytes or blast cells were obtained by fluorescence-activated cell sorting with the monoclonal antibody WEM-G11. These populations were used to study the effect of pulse stimulation by purified recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) or cross-reacting purified murine granulocyte colony-stimulating factor (G- CSF). Maximal clone formation by promyelocytes and myelocytes was observed in 1-mL agar cultures stimulated continuously with 400 units of either CSF and in cultures of cells that were pulse stimulated by 3,200 units (or greater) of either CSF. Pulse stimulation by 800 units of GM-CSF or G-CSF generated 75% clone formation, and pulse stimulation by 200 units CSF gave 50% clone formation. The majority of clones formed by pulse-stimulated cells were only two cells in size; however, some clones were up to 15 cells in size after a single exposure to CSF. Clone formation was not observed in cultures of blast cell populations after a single pulse stimulation with GM-CSF or G-CSF.

scholarly journals Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jani Lappalainen ◽  
Nicolas Yeung ◽  
Su D. Nguyen ◽  
Matti Jauhiainen ◽  
Petri T. Kovanen ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Foam Cells ◽  
Colony Stimulating Factor ◽  
Human Macrophages ◽  
Gm Csf ◽  
Macrophage Subpopulations ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

AbstractIn atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte–macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in the presence of either M-CSF or GM-CSF to obtain M-MØ and GM-MØ, respectively. The macrophages were converted into cholesterol-loaded foam cells by incubating them with acetyl-LDL, and their atheroinflammatory gene expression profiles were then assessed. Compared with GM-MØ, the M-MØ expressed higher levels of CD36, SRA1, and ACAT1, and also exhibited a greater ability to take up acetyl-LDL, esterify cholesterol, and become converted to foam cells. M-MØ foam cells expressed higher levels of ABCA1 and ABCG1, and, correspondingly, exhibited higher rates of cholesterol efflux to apoA-I and HDL2. Cholesterol loading of M-MØ strongly suppressed the high baseline expression of CCL2, whereas in GM-MØ the low baseline expression CCL2 remained unchanged during cholesterol loading. The expression of TNFA, IL1B, and CXCL8 were reduced in LPS-activated macrophage foam cells of either subtype. In summary, cholesterol loading converged the CSF-dependent expression of key genes related to intracellular cholesterol balance and inflammation. These findings suggest that transformation of CSF-polarized macrophages into foam cells may reduce their atheroinflammatory potential in atherogenesis.

scholarly journals Construction of Recombinant Human GM-CSF and GM-CSF-ApoA-I Fusion Protein and Evaluation of Their Biological Activity

2021 ◽  
Vol 14 (5) ◽  
pp. 459
Author(s):  
Mariya Pykhtina ◽  
Svetlana Miroshnichenko ◽  
Vladimir Romanov ◽  
Antonina Grazhdantseva ◽  
Galina Kochneva ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
E Coli ◽  
Gm Csf ◽  
Human Apolipoprotein ◽  
Proliferative Effect ◽  
Erythroleukemia Cells ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

In this study, two strains of the yeast P. pastoris were constructed, one of which produced authentic recombinant human granulocyte-macrophage colony-stimulating factor (ryGM-CSF), and the other was a chimera consisting of ryGM-CSF genetically fused with mature human apolipoprotein A-I (ApoA-I) (ryGM-CSF-ApoA-I). Both forms of the cytokine were secreted into the culture medium. The proteins’ yield during cultivation in flasks was 100 and 60 mg/L for ryGM-CSF and ryGM-CSF-ApoA-I, respectively. Both forms of recombinant GM-CSF stimulated the proliferation of human TF-1 erythroleukemia cells; however, the amount of chimera required was 10-fold that of authentic GM-CSF to induce a similar proliferative effect. RyGM-CSF exhibited a 2-fold proliferative effect on BFU-E (burst-forming units—erythroid) at a concentration 1.7 fold less than non-glycosylated E. coli-derived GM-CSF. The chimera together with authentic ryGM-CSF increased the number of both erythroid precursors and BMC granulocytes after 48 h of incubation of human bone marrow cells (BMCs). In addition, the chimeric form of ryGM-CSF was more effective at increasing the viability of the total amount of BMCs, decreasing apoptosis compared to the authentic form. ryGM-CSF-ApoA-I normalized the proliferation, maturation, and segmentation of neutrophils within the physiological norm, preserving the pool of blast cells under conditions of impaired granulopoiesis. The chimera form of GM-CSF exhibited the properties of a multilinear growth factor, modulating the activity of GM-CSF and, perhaps, it may be more suitable for the normalization of granulopoiesis.

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