Hematopoietic growth factors activate the tyrosine phosphorylation of distinct sets of proteins in interleukin-3-dependent murine cell lines

1988 ◽  
Vol 8 (5) ◽  
pp. 2214-2218
Author(s):  
A O Morla ◽  
J Schreurs ◽  
A Miyajima ◽  
J Y Wang
Keyword(s):  
Growth Factors ◽  
Tyrosine Phosphorylation ◽  
Cell Lines ◽  
Interleukin 2 ◽  
Interleukin 4 ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Growth Factors ◽  
Transient Event ◽  
Interleukin 3 ◽  
Macrophage Colony

By immunoblotting with antibodies for phosphotyrosine, we have demonstrated that the hematopoietic growth factors interleukin-2, interleukin-3, interleukin-4, and granulocyte-macrophage colony-stimulating factor stimulate the tyrosine phosphorylation of specific sets of proteins in murine hematopoietic progenitor cell lines. The stimulation of tyrosine phosphorylation is a receptor-dependent transient event. The effect of these hematopoietic growth factors on protein tyrosine phosphorylation was not mediated through protein kinase C.

scholarly journals Hematopoietic growth factors activate the tyrosine phosphorylation of distinct sets of proteins in interleukin-3-dependent murine cell lines.

1988 ◽  
Vol 8 (5) ◽  
pp. 2214-2218 ◽  
Author(s):  
A O Morla ◽  
J Schreurs ◽  
A Miyajima ◽  
J Y Wang
Keyword(s):  
Growth Factors ◽  
Tyrosine Phosphorylation ◽  
Cell Lines ◽  
Interleukin 2 ◽  
Interleukin 4 ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Growth Factors ◽  
Transient Event ◽  
Interleukin 3 ◽  
Macrophage Colony

By immunoblotting with antibodies for phosphotyrosine, we have demonstrated that the hematopoietic growth factors interleukin-2, interleukin-3, interleukin-4, and granulocyte-macrophage colony-stimulating factor stimulate the tyrosine phosphorylation of specific sets of proteins in murine hematopoietic progenitor cell lines. The stimulation of tyrosine phosphorylation is a receptor-dependent transient event. The effect of these hematopoietic growth factors on protein tyrosine phosphorylation was not mediated through protein kinase C.

scholarly journals Response patterns of purified myeloma cells to hematopoietic growth factors

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1915-1924 ◽  
Author(s):  
KC Anderson ◽  
RM Jones ◽  
C Morimoto ◽  
P Leavitt ◽  
BA Barut
Keyword(s):  
Growth Factors ◽  
Cell Lines ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Interleukin 1 ◽  
Interleukin 2 ◽  
Interleukin 4 ◽  
Hematopoietic Growth Factors ◽  
Myeloma Cells

Abstract Tumor cells were isolated from the bone marrow of seven patients with multiple myeloma and from the peripheral blood of three patients with plasma cell leukemia using Ficoll-Hypaque (FH) density sedimentation followed by immune rosette depletion of T, myeloid, monocytoid, and natural killer (NK) cells. Enrichment to greater than or equal to 93% plasma cells was confirmed with Wright's-Giemsa staining, with intracytoplasmic immunoglobulin staining, and with staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, monocytoid, and myeloma antigens in indirect immunofluorescence assays. Myeloma cells neither proliferated nor secreted Ig in response to G/M-CSF, G- CSF, M-CSF, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), or interleukin-4 (IL-4). Significant proliferation (SI greater than or equal to 3.0) was induced by interleukin-6 (IL-6) in six of ten patients (SI of 31 and 43 in two cases); and to interleukin-3 (IL-3) and interleukin-5 (IL-5), independently, in two patients each. Peak proliferation to IL-5 or IL-6 and to IL-3 occurred in cells pulsed with 3[H] thymidine at 24 and 48 hours, respectively; and proliferation to combinations of factors did not exceed that noted to IL-6 alone; Ig secretion was not documented under any culture conditions. Three myeloma-derived cell lines similarly studied demonstrated variable responses. The heterogeneity in the in vitro responses of myeloma cells and derived cell lines to exogenous growth factors enhances our understanding of abnormal plasma cell growth and may yield insight into the pathophysiology of plasma cell dyscrasias.

scholarly journals Response patterns of purified myeloma cells to hematopoietic growth factors

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1915-1924 ◽  
Author(s):  
KC Anderson ◽  
RM Jones ◽  
C Morimoto ◽  
P Leavitt ◽  
BA Barut
Keyword(s):  
Growth Factors ◽  
Cell Lines ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Interleukin 1 ◽  
Interleukin 2 ◽  
Interleukin 4 ◽  
Hematopoietic Growth Factors ◽  
Myeloma Cells

Tumor cells were isolated from the bone marrow of seven patients with multiple myeloma and from the peripheral blood of three patients with plasma cell leukemia using Ficoll-Hypaque (FH) density sedimentation followed by immune rosette depletion of T, myeloid, monocytoid, and natural killer (NK) cells. Enrichment to greater than or equal to 93% plasma cells was confirmed with Wright's-Giemsa staining, with intracytoplasmic immunoglobulin staining, and with staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, monocytoid, and myeloma antigens in indirect immunofluorescence assays. Myeloma cells neither proliferated nor secreted Ig in response to G/M-CSF, G- CSF, M-CSF, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), or interleukin-4 (IL-4). Significant proliferation (SI greater than or equal to 3.0) was induced by interleukin-6 (IL-6) in six of ten patients (SI of 31 and 43 in two cases); and to interleukin-3 (IL-3) and interleukin-5 (IL-5), independently, in two patients each. Peak proliferation to IL-5 or IL-6 and to IL-3 occurred in cells pulsed with 3[H] thymidine at 24 and 48 hours, respectively; and proliferation to combinations of factors did not exceed that noted to IL-6 alone; Ig secretion was not documented under any culture conditions. Three myeloma-derived cell lines similarly studied demonstrated variable responses. The heterogeneity in the in vitro responses of myeloma cells and derived cell lines to exogenous growth factors enhances our understanding of abnormal plasma cell growth and may yield insight into the pathophysiology of plasma cell dyscrasias.

scholarly journals Production of growth factors by malignant lymphoma cell lines

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 572-578
Author(s):  
M Tweeddale ◽  
N Jamal ◽  
A Nguyen ◽  
XH Wang ◽  
MD Minden ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Malignant Lymphoma ◽  
Cell Lines ◽  
Colony Formation ◽  
Cell Function ◽  
Colony Growth ◽  
Interleukin 4 ◽  
Hematopoietic Growth Factors ◽  
Barr Virus

Fourteen Epstein-Barr virus (EBV)-negative cell lines were raised from bone marrow (BM), peripheral blood (PB), or lymph node samples of patients with intermediate- or high-grade malignant lymphoma. The cell lines were propagated in liquid suspension culture. They contain clonogenic progenitors capable of forming lymphoma colonies in semi- solid culture medium. Cells of these lines were used to examine the growth factor requirements of their clonogenic progenitors and to assess their ability to produce their own growth factors. Two of the cell lines (OCI-Ly9 and OCI-Ly13.1) required addition of exogenous factors for colony growth. These factors were routinely provided by media conditioned by phytohemagglutinin-stimulated leukocytes (PHA- LCM). Three lines formed some and nine lines gave rise to optimal numbers of colonies without addition of growth factors. Eight of these factor-independent lines were able to function as feeder cells and promoted colony formation by both factor-dependent lines. Cell lines that displayed feeder cell function released activities into supernatants able to replace their cellular source. Some of these endogenously produced growth-promoting activities could be replaced by known hematopoietic growth factors. Both factor-dependent cell lines were cultured with recombinant IL-1 alpha, IL-2, IL-3, IL-6, and GM colony-stimulating factor (CSF) and semipurified B-cell growth factor (BCGF) interleukin-4 (IL-4). A heterogeneous response pattern was observed. Both lines formed colonies with IL-4. The colonies were comparable in frequency and size with colonies observed with (PHA-LCM). OCI-Ly9 responded to IL-6 but showed no growth with IL-2. In contrast, the TAC-positive line OCI-Ly13.1 gave rise to colonies with IL-2 while remaining unresponsive to IL-6. A moderate number of colonies was observed when cells of this line were cultured with GM-CSF. Colony formation of both lines was uninfluenced by IL1 alpha or IL-3.

scholarly journals Activation of the Stress-Activated Protein Kinases by Multiple Hematopoietic Growth Factors With the Exception of Interleukin-4

Blood ◽  
1997 ◽  
Vol 89 (9) ◽  
pp. 3092-3096 ◽  
Author(s):  
Ian N. Foltz ◽  
John W. Schrader
Keyword(s):  
Growth Factors ◽  
Immune System ◽  
Protein Kinases ◽  
Activated Protein C ◽  
Interleukin 4 ◽  
Hematopoietic Growth Factors ◽  
Growth And Survival ◽  
Gm Csf ◽  
Macrophage Colony ◽  
And Function

Abstract The stress-activated protein/c-Jun N-terminal kinases (SAPK/JNK) have been shown to be activated by pro-inflammatory cytokines, as well as physical and chemical stresses. We now show that a variety of hematopoietic growth factors, including Steel locus factor (SLF ), granulocyte-macrophage colony-stimulating factor (GM-CSF ), and interleukin-3 (IL-3), all of which promote the growth and survival of various lineages of hematopoietic cells, activate the stress-activated protein kinases in the factor-dependent cell line MC/9. These hematopoietic growth factors activated both 46- and 55-kD isoforms of both SAPKγ and SAPKα. Furthermore, we demonstrate that SAPK activation correlated with the phosphorylation of SAPK/ERK kinase-1 (SEK1) after treatment with SLF or GM-CSF. Interestingly, IL-4, a cytokine with distinctive and important effects on the immune system, was the exception among the hematopoietic growth factors we examined in failing to induce activation of SAPKγ, SAPKα, or SEK1. These findings show that activation of SAPK is involved, not only in responses to stresses, but also in signaling by growth factors that regulate the normal development and function of cells of the immune system.

scholarly journals Activation and growth of colony-stimulating factor-dependent cell lines is cell cycle stage dependent.

1987 ◽  
Vol 166 (5) ◽  
pp. 1419-1435 ◽  
Author(s):  
L London ◽  
J P McKearn
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Dependent Cell ◽  
G0 Phase ◽  
Macrophage Colony ◽  
Stimulating Factor

Hematopoietic cell development is regulated by a series of growth factors that are progressively restricted in their biological activity. IL-3 is a multi-lineage growth factor that supports the growth and differentiation of progenitor cells belonging to multiple lineages. However, the mechanism by which IL-3 induces proliferation and differentiation of these cells is not completely understood. In this report, we have used two IL-3-dependent cell lines, FDC-P1 (a myeloid progenitor) and F15.12 (a lymphoid progenitor) to investigate IL-3-mediated growth and differentiation. When either FDC-P1 or FL5.12 cells are deprived of IL-3, greater than 90% of all cells accumulate in the G0 phase of the cell cycle. Upon readdition of IL-3, the cells will reenter the active phases of the cell cycle. Therefore, IL-3 can act as both a competence (G0----G1) factor, and a progression (G1----M) factor for hematopoietic precursor clones. FDC-P1 cells can also proliferate in response to granulocyte/macrophage colony-stimulating factor (G/M-CSF) and IL-4 (B cell stimulatory factor 1 [BSF-1]). However, resting (G0) FDC-P1 cells have lost their ability to grow in response to both G/M-CSF and IL-4, even though both factors can induce a G0----G1 transition. Therefore, G/M-CSF or IL-4 behave as progression factors among certain IL-3-responsive clones, and in those cases only in defined points in the cell cycle. Both IL-4 and G/M-CSF can maintain long-term growth of FDC-P1 cells. Upon removal of factor for 24 h, these clones accumulate in the G1 phase of the cell cycle and do not appear to enter G0 even after 36 h of factor deprivation. Therefore, cells maintained in G/M-CSF or IL-4 have altered growth requirements compared with the IL-3-dependent lines from which they were derived. The ability of various hematopoietic growth factors to regulate cell cycle progression in IL-3-dependent cell lines is dependent not only upon the lineage from which these cells were derived, but also the phase of the cell cycle in which those cells reside. The consequences of these interactions dictate the manner by which various clones will respond to CSFs and whether the cells will grow and/or differentiate.

scholarly journals Rapid priming of human monocytes by human hematopoietic growth factors: granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, and interleukin-3 selectively enhance superoxide release triggered by receptor-mediated agonists

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1553-1557 ◽  
Author(s):  
A Yuo ◽  
S Kitagawa ◽  
K Motoyoshi ◽  
E Azuma ◽  
M Saito ◽  
...  
Keyword(s):  
Growth Factors ◽  
Human Monocytes ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Con A ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The effects of hematopoietic growth factors on human monocyte superoxide (O2-) release were investigated by using purified human monocytes in suspension. Among growth factors studied, granulocyte- macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (M-CSF), and interleukin-3 (IL-3) primed human monocytes and enhanced O2- release stimulated by the receptor-mediated agonists, N-formyl- methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate, which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of cells with 1 to 5 ng/mL (0.07 to 0.34 nmol/L) GM-CSF, 50 to 100 ng/mL (0.5 to 1.1 nmol/L) M-CSF, or 10 to 20 ng/mL (0.6 to 1.3 nmol/L) IL-3 for 10 minutes at 37 degrees C. Potency of the maximal priming effects on FMLP- or Con A-induced O2- release was GM-CSF greater than M- CSF = IL-3. The combination of the optimal concentrations of any two CSFs resulted in the effect of more potent priming agent alone. Enhancement of O2- release by GM-CSF was observed over the complete range of effective concentrations of FMLP (10(-8) to 10(-6) mol/L). The pretreatment of monocytes with granulocyte-CSF (50 ng/mL), interferon- gamma (1,000 U/mL), or IL-4 (20 ng/mL) for 10 minutes at 37 degrees C had no effect on O2- release stimulated by FMLP or Con A. These findings show that GM-CSF, M-CSF, and IL-3 selectively enhance O2- release in human monocytes triggered by receptor-mediated agonists after short-term preincubation.

scholarly journals Production of growth factors by malignant lymphoma cell lines

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 572-578 ◽  
Author(s):  
M Tweeddale ◽  
N Jamal ◽  
A Nguyen ◽  
XH Wang ◽  
MD Minden ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Malignant Lymphoma ◽  
Cell Lines ◽  
Colony Formation ◽  
Cell Function ◽  
Colony Growth ◽  
Interleukin 4 ◽  
Hematopoietic Growth Factors ◽  
Barr Virus

Abstract Fourteen Epstein-Barr virus (EBV)-negative cell lines were raised from bone marrow (BM), peripheral blood (PB), or lymph node samples of patients with intermediate- or high-grade malignant lymphoma. The cell lines were propagated in liquid suspension culture. They contain clonogenic progenitors capable of forming lymphoma colonies in semi- solid culture medium. Cells of these lines were used to examine the growth factor requirements of their clonogenic progenitors and to assess their ability to produce their own growth factors. Two of the cell lines (OCI-Ly9 and OCI-Ly13.1) required addition of exogenous factors for colony growth. These factors were routinely provided by media conditioned by phytohemagglutinin-stimulated leukocytes (PHA- LCM). Three lines formed some and nine lines gave rise to optimal numbers of colonies without addition of growth factors. Eight of these factor-independent lines were able to function as feeder cells and promoted colony formation by both factor-dependent lines. Cell lines that displayed feeder cell function released activities into supernatants able to replace their cellular source. Some of these endogenously produced growth-promoting activities could be replaced by known hematopoietic growth factors. Both factor-dependent cell lines were cultured with recombinant IL-1 alpha, IL-2, IL-3, IL-6, and GM colony-stimulating factor (CSF) and semipurified B-cell growth factor (BCGF) interleukin-4 (IL-4). A heterogeneous response pattern was observed. Both lines formed colonies with IL-4. The colonies were comparable in frequency and size with colonies observed with (PHA-LCM). OCI-Ly9 responded to IL-6 but showed no growth with IL-2. In contrast, the TAC-positive line OCI-Ly13.1 gave rise to colonies with IL-2 while remaining unresponsive to IL-6. A moderate number of colonies was observed when cells of this line were cultured with GM-CSF. Colony formation of both lines was uninfluenced by IL1 alpha or IL-3.

scholarly journals Rapid priming of human monocytes by human hematopoietic growth factors: granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, and interleukin-3 selectively enhance superoxide release triggered by receptor-mediated agonists

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1553-1557
Author(s):  
A Yuo ◽  
S Kitagawa ◽  
K Motoyoshi ◽  
E Azuma ◽  
M Saito ◽  
...  
Keyword(s):  
Growth Factors ◽  
Human Monocytes ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Con A ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The effects of hematopoietic growth factors on human monocyte superoxide (O2-) release were investigated by using purified human monocytes in suspension. Among growth factors studied, granulocyte- macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (M-CSF), and interleukin-3 (IL-3) primed human monocytes and enhanced O2- release stimulated by the receptor-mediated agonists, N-formyl- methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate, which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of cells with 1 to 5 ng/mL (0.07 to 0.34 nmol/L) GM-CSF, 50 to 100 ng/mL (0.5 to 1.1 nmol/L) M-CSF, or 10 to 20 ng/mL (0.6 to 1.3 nmol/L) IL-3 for 10 minutes at 37 degrees C. Potency of the maximal priming effects on FMLP- or Con A-induced O2- release was GM-CSF greater than M- CSF = IL-3. The combination of the optimal concentrations of any two CSFs resulted in the effect of more potent priming agent alone. Enhancement of O2- release by GM-CSF was observed over the complete range of effective concentrations of FMLP (10(-8) to 10(-6) mol/L). The pretreatment of monocytes with granulocyte-CSF (50 ng/mL), interferon- gamma (1,000 U/mL), or IL-4 (20 ng/mL) for 10 minutes at 37 degrees C had no effect on O2- release stimulated by FMLP or Con A. These findings show that GM-CSF, M-CSF, and IL-3 selectively enhance O2- release in human monocytes triggered by receptor-mediated agonists after short-term preincubation.

scholarly journals Various human hematopoietic growth factors (interleukin-3, GM-CSF, G- CSF) stimulate clonal growth of nonhematopoietic tumor cells [see comments]

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 80-83 ◽  
Author(s):  
WE Berdel ◽  
S Danhauser-Riedl ◽  
G Steinhauser ◽  
EF Winton
Keyword(s):  
Growth Factors ◽  
Cell Lines ◽  
Clonal Growth ◽  
Human Tumor ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Malignant Cell ◽  
Hematopoietic Growth Factors ◽  
Interleukin 3

Abstract We have studied the effect of recombinant human hematopoietic growth factors (interleukin-3 [rhIL-3], granulocyte-macrophage colony- stimulating factor [rhGM-CSF], and granulocyte CSF [rhG-CSF]) on the clonal growth of human colon adenocarcinoma cell lines HTB-38, CCL 187, and WiDr (CCL 218). The factors stimulated clonal growth of HTB-38 and CCL 187 in a capillary modification of the human tumor clonogenic assay in agar up to twofold. There were dose-response correlations over a range of 1 to 10,000 U/mL for rhIL-3, rhGM-CSF, and rhG-CSF. Incubation with neutralizing monoclonal antibodies abolished the stimulation of clonal growth by rhGM-CSF. The WiDr cell line was nonresponsive to rhIL- 3 and rhGM-CSF. These results represent the first evidence that a variety of hematopoietic growth factors can stimulate the growth of clonogenic cells of some nonhematopoietic malignant cell lines in vitro.

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