scholarly journals Recombinant gibbon interleukin-3 acts synergistically with recombinant human G-CSF and GM-CSF in vitro

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1596-1600 ◽  
Author(s):  
RL Paquette ◽  
JY Zhou ◽  
YC Yang ◽  
SC Clark ◽  
HP Koeffler
Keyword(s):  
Colony Formation ◽  
Clinical Utility ◽  
Bone Marrow Cells ◽  
Soft Agar ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Normal Human ◽  
Stimulating Factor ◽  
Normal Human Bone Marrow

Recombinant gibbon interleukin-3 (IL-3) is a multilineage hematopoietic colony-stimulating factor (CSF) that recently was cloned and found to be highly homologous with human IL-3. Gibbon IL-3, as well as human granulocyte-CSF (G-CSF) and human granulocyte-macrophage CSF (GM-CSF), stimulated normal human bone marrow cells to form myeloid colonies in soft agar in a sigmoidal dose-response manner. When IL-3 was added to increasing concentrations of G-CSF or GM-CSF, synergistic colony formation occurred as compared with the effects of each CSF alone. Synergism was also noted when G-CSF was added with GM-CSF and when all the CSFs were added simultaneously. The combination of IL-3 and GM-CSF was less stimulatory than all the other CSF combinations. At day 11 of culture, IL-3 induced granulocyte-macrophage (38%), eosinophil (30%), granulocyte (18%), and macrophage (14%) colony formation. In summary, gibbon IL-3 is a growth factor that can synergize with other CSFs to enhance proliferation of myeloid-committed progenitors, suggesting that combinations of CSFs may have clinical utility in patients with neutropenia of various etiologies.

scholarly journals Recombinant gibbon interleukin-3 acts synergistically with recombinant human G-CSF and GM-CSF in vitro

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1596-1600 ◽  
Author(s):  
RL Paquette ◽  
JY Zhou ◽  
YC Yang ◽  
SC Clark ◽  
HP Koeffler
Keyword(s):  
Colony Formation ◽  
Clinical Utility ◽  
Bone Marrow Cells ◽  
Soft Agar ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Normal Human ◽  
Stimulating Factor ◽  
Normal Human Bone Marrow

Abstract Recombinant gibbon interleukin-3 (IL-3) is a multilineage hematopoietic colony-stimulating factor (CSF) that recently was cloned and found to be highly homologous with human IL-3. Gibbon IL-3, as well as human granulocyte-CSF (G-CSF) and human granulocyte-macrophage CSF (GM-CSF), stimulated normal human bone marrow cells to form myeloid colonies in soft agar in a sigmoidal dose-response manner. When IL-3 was added to increasing concentrations of G-CSF or GM-CSF, synergistic colony formation occurred as compared with the effects of each CSF alone. Synergism was also noted when G-CSF was added with GM-CSF and when all the CSFs were added simultaneously. The combination of IL-3 and GM-CSF was less stimulatory than all the other CSF combinations. At day 11 of culture, IL-3 induced granulocyte-macrophage (38%), eosinophil (30%), granulocyte (18%), and macrophage (14%) colony formation. In summary, gibbon IL-3 is a growth factor that can synergize with other CSFs to enhance proliferation of myeloid-committed progenitors, suggesting that combinations of CSFs may have clinical utility in patients with neutropenia of various etiologies.

CIAPIN1 is a potential target for apoptosis of multiple myeloma

2019 ◽  
Vol 9 (9) ◽  
pp. 1106-1111
Author(s):  
Xiao-Bo Wang ◽  
Le-Ping Yan ◽  
Li-Hua Yuan ◽  
Bo Lu ◽  
Dong-Jun Lin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Xenograft Model ◽  
Soft Agar ◽  
Normal Human ◽  
Related Proteins

This study firstly aimed to reveal the gene expression differences of CIAPIN1 between myelomas cells from bone marrow cells of multiple myeloma patients and normal human, and subsequently investigate the regulation role of this gene on tumorigenicity ability of multiple myeloma (MM) cell line U266 via in vitro colony formation and in vivo xenograft studies. RT-PCR results obtained from 18 MM patients and 10 health people showed that the expression of CIAPIN1 gene was 4 times higher in normal human compared to MM patients. Besides, CIAPIN1 siRNA (si-CIAPIN1) transfected U266 cells presented higher proliferation ratio and superior colony forming ability than U266 cells and U266 cells transfected with non-coding siRNA (controls) evaluated by CCK8 test and soft agar colony formation assay, respectively. In a mice MM xenograft model, the si-CIAPIN1 transfected U266 cells induced the biggest tumor compared to the controls. Furthermore, CIAPIN1 overexpressed U266 cells were developed and compared with the si-CIAPIN1 transfected U266 cells to study the role of CIAPIN1 in the production of apoptosis related proteins in U266 cells. Results indicated that CIAPIN1 facilitated apoptosis promoting proteins expression in U266 cells, such as upregulation of BAX, BAK, Bcl-xs and BIM, and downregulation of p38, PKC, Bcl-2 and Bcl-xl proteins. Therefore, CIAPIN1 can be a potential suppression target gene in multiple myeloma.

Interleukin-4 suppresses the interleukin-3 dependent erythroid colony formation from normal human bone marrow cells

1990 ◽  
Vol 74 (3) ◽  
pp. 246-250 ◽  
Author(s):  
Joost Th. M. de Wolf ◽  
John A. M. Beentjes ◽  
Mariet T. Esselink ◽  
Jan W. Smit ◽  
M. Ruud Halie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Interleukin 4 ◽  
Interleukin 3 ◽  
Normal Human ◽  
Normal Human Bone Marrow ◽  
Marrow Cells

Effect of G-CSF and M-CSF on the in vitro Toxicity Associated with Zidovudine in Normal Human Bone Marrow Haematopoietic Progenitor Stem Cells

1993 ◽  
Vol 4 (6) ◽  
pp. 309-313 ◽  
Author(s):  
V. S. Gallicchio ◽  
N. K. Hughes
Keyword(s):  
Bone Marrow ◽  
Colony Formation ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Colony Stimulating Factor ◽  
Erythroid Progenitor ◽  
Normal Human ◽  
Stimulating Factor ◽  
Normal Human Bone Marrow

Zidovudine, the antiviral drug used in the treatment of acquired immunodeficiency syndrome (AIDS), causes toxicity to the haematopoietic system. Although use of the haematopoietic growth factors, GM-CSF and erythropoietin have been investigated in clinical trials to modulate antiviral toxicity, there is scant data which supports their ability to ameliorate zidovudine induced toxicity on haematopoietic progenitor cells when combined in vitro. We describe here the results of studies designed to evaluate the capacity of additional haematopoietic factors such as granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) to modulate zidovudine-induced toxicity on G-CSF and M-CSF dependent-colony formation in the presence or absence of zidovudine in vitro. These factors were also studied combined with erythropoietin in culture for the early erythroid progenitor BFU-E using adherent, T-cell, depleted normal human bone marrow cells in the presence or absence of zidovudine. In the presence of zidovudine at the concentration producing 50% inhibition of G- and M-CSF dependent colony formation, (5 × 10−5M), dose-escalation of either G-CSF or M-CSF failed to ameliorate zidovudine toxicity. However, in the presence of zidovudine at the concentration that produces 50% inhibition of BFU-E (5 × 10−9M), and optimal erythropoietin (1 unit ml−1), G-CSF ameliorated zidovudine inhibition of BFU-E, which was not observed with M-CSF. In the presence of erythropoietin, G-CSF increased significantly normal BFU-E. These studies indicate that G-CSF may be useful in ameliorating zidovudine-induced anaemia and suggest G-CSF may act as a synergistic factor to enhance erythropoietin to support the growth of erythroid progenitors in conditions where erythropoitin is ineffective.

scholarly journals Interleukin-3 is significantly more effective than other colony- stimulating factors in long-term maintenance of human bone marrow- derived colony-forming cells in vitro

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1836-1841 ◽  
Author(s):  
M Kobayashi ◽  
BH Van Leeuwen ◽  
S Elsbury ◽  
ME Martinson ◽  
IG Young ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cultured Cells ◽  
Bone Marrow Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Factor G ◽  
Marrow Cells

Abstract Human bone marrow cells cultured for 21 days in the presence of recombinant human interleukin-3 (IL-3) produced up to 28 times more colony-forming cells (CFC) than could be obtained from cultures stimulated with granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF). IL-3-cultured cells retained a multipotent response to IL-3 in colony assays but were restricted to formation of granulocyte colonies in G-CSF and granulocyte or macrophage colonies in GM-CSF. Culture of bone marrow cells in IL-3 also led to accumulation of large numbers of eosinophils and basophils. These data contrast with the effects of G-CSF, GM-CSF, and IL-3 in seven-day cultures. Here both GM-CSF and IL-3 amplified total CFC that had similar multipotential colony-forming capability in either factor. G-CSF, on the other hand, depleted IL-3-responsive colony-forming cells dramatically, apparently by causing these cells to mature into granulocytes. The data suggest that a large proportion of IL-3- responsive cells in human bone marrow express receptors for G-CSF and can respond to this factor, the majority becoming neutrophils. Furthermore, the CFC maintained for 21 days in IL-3 may be a functionally distinct population from that produced after seven days culture of bone marrow cells in either IL-3 or GM-CSF.

scholarly journals Myeloid differentiation of purified CD34+ cells after stimulation with recombinant human granulocyte-monocyte colony-stimulating factor (CSF), granulocyte-CSF, monocyte-CSF, and interleukin-3

Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3192-3199 ◽  
Author(s):  
T Egeland ◽  
R Steen ◽  
H Quarsten ◽  
G Gaudernack ◽  
YC Yang ◽  
...  
Keyword(s):  
Myeloid Differentiation ◽  
Cell Multiplication ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Proliferation And Differentiation ◽  
Stimulating Factor

Abstract CD34+ cells isolated from bone marrow or umbilical cord blood from healthy donors were studied for proliferation and differentiation in liquid cultures in the presence of recombinant human granulocyte- monocyte colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), monocyte CSF (M-CSF), and interleukin-3 (IL-3), followed by immunophenotyping for myeloid and myeloid-associated cell surface markers. IL-3, either alone or together with GM-CSF, G-CSF, or M-CSF, induced, on average, 50-fold cell multiplication, GM-CSF five fold to 10-fold, and G-CSF and M-CSF less than fivefold. Cells from cultures stimulated with GM-CSF, G-CSF, or M-CSF alone contained cells with a “broad” myeloid profile, “broader” than observed in cultures with IL-3. However, since IL-3 induced rapid cell multiplication, high numbers of cells expressing early (CD13, CD33) and late myeloid markers (CD14, CD15) were recovered. The presence of other CSFs together with IL-3 did not alter the IL-3-induced effect on the cells. When 5,000 CD34+ cells were cultured with IL-3 alone, the cultures still contained 2,000 to 5,000 CD34+ cells after 14 days of culture, while cells cultured with GM-CSF, G-CSF, or M-CSF contained less than 1,000 CD34+ cells. Furthermore, 1,000 to 3,000 cells were positive for the megakaryocytic lineage marker CD41b after cultures with GM-CSF or IL-3, while cultures with G-CSF or M-CSF did not contain detectable numbers of CD41b+ cells. Finally, erythroid cells could also be generated from purified CD34+ cells. The results show that IL-3 and GM-CSF can induce rapid proliferation of purified CD34+ cells in vitro with differentiation to multiple myeloid lineages, while certain subsets maintain expression of CD34.

scholarly journals Characterization of the human burst-forming unit-megakaryocyte

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 145-151 ◽  
Author(s):  
RA Briddell ◽  
JE Brandt ◽  
JE Straneva ◽  
EF Srour ◽  
R Hoffman
Keyword(s):  
Colony Formation ◽  
Progenitor Cell ◽  
Recombinant Erythropoietin ◽  
Hematopoietic Growth Factors ◽  
Gm Csf ◽  
Hla Dr ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Two classes of human marrow megakaryocyte progenitor cells are described. Colony-forming unit-megakaryocyte (CFU-MK)-derived colonies appeared in vitro after 12-day incubation; burst-forming unit- megakaryocyte (BFU-MK)-derived colonies appeared after 21 days. CFU-MK- derived colonies were primarily unifocal and composed of 11.6 +/- 1.2 cells/colony; BFU-MK-derived colonies were composed of 2.3 +/- 0.4 foci and 108.6 +/- 4.4 cells/colony. CFU-MK and BFU-MK were separable by counterflow centrifugal elutriation. CFU-MK colony formation was diminished by exposure to 5-fluorouracil (5-FU); BFU-MK colony formation was unaffected. CFU-MK and BFU-MK were immunologically phenotyped. CFU-MK expressed the human progenitor cell antigen-1 (HPCA- 1, CD34, clone My10) and a major histocompatibility class II locus, HLA- DR, and BFU-MK expressed only detectable amounts of CD34. BFU-MK colony formation was entirely dependent on addition of exogenous hematopoietic growth factors. Recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) possessed such colony- stimulating activity, whereas recombinant erythropoietin (Epo), G-CSF, IL-1 alpha, IL-4, and purified thrombocytopoiesis-stimulating factor did not. These studies indicate the existence of a human megakaryocyte progenitor cell, the BFU-MK, which has unique properties allowing it to be distinguished from the CFU-MK.

scholarly journals Target cells for granulocyte colony-stimulating factor, interleukin-3, and interleukin-5 in differentiation pathways of neutrophils and eosinophils

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1956-1961 ◽  
Author(s):  
H Ema ◽  
T Suda ◽  
K Nagayoshi ◽  
Y Miura ◽  
CI Civin ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Early Stage ◽  
Target Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Cd34 Antigen ◽  
Cd34 Cells ◽  
Stimulating Factor

Abstract To study the relationship between hematopoietic factors and their responsive hematopoietic progenitors in the differentiation process, both purified factors and enriched progenitors are required. We isolated total CD34+ cells, CD34+,CD33+ cells, and CD34+,CD33- cells individually from normal human bone marrow cells by fluorescence- activated cell sorter (FACS), and examined the effects of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), and IL-5 on in vitro colony formation of these cells. CD34+,CD33+ cells formed granulocyte colonies in the presence of G-CSF. Both CD34+,CD33+ cells and CD34+,CD33- cells formed granulocyte/macrophage colonies in the presence of IL-3. Eosinophil (Eo) colonies were only formed by CD34+,CD33- cells in response to IL-3, but scarcely formed by CD34+ cells in the presence of IL-5. We performed the two-step cultures consisting of the primary liquid culture for 6 days and the secondary methylcellulose culture, and serially examined changes in phenotypes of ,he cells cultured in the primary culture. CD34-,CD33+ cells derived from CD34+,CD33+ cells by preincubation with G-CSF or IL-3 formed Eo colonies in the presence of IL-5 but not IL-3. CD34-,CD33+ cells derived from CD34+,CD33- cells by preincubation with IL-3 also formed Eo colonies by support of IL-5 as well as IL-3. Both CD34+ cells gradually lost the CD34 antigen by day 6 of incubation with G-CSF or IL- 3. Loss of this antigen was well-correlated with acquisition of susceptibility to IL-5. It was concluded that G-CSF supported the neutrophil differentiation of committed colony-forming cells, IL-3 supported that of both committed and multipotent colony-forming cells. G-CSF and IL-3 also supported the early stage of E. differentiation; IL- 5 supported the late stage of that.

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