scholarly journals Alterations in differentiation and behavior of monocytic phagocytes in transgenic mice that express dominant suppressors of ras signaling.

1995 ◽  
Vol 15 (2) ◽  
pp. 693-703 ◽  
Author(s):  
D I Jin ◽  
S B Jameson ◽  
M A Reddy ◽  
D Schenkman ◽  
M C Ostrowski
Keyword(s):  
Peritoneal Macrophages ◽  
Proximal Promoter ◽  
Ras Signaling ◽  
Colony Stimulating Factor ◽  
Monocytic Cells ◽  
And Behavior ◽  
Stimulating Factor

To address the role of ras signaling in monocytic phagocytes in vivo, the expression of two dominant suppressors of in vitro ras signaling pathways, the carboxyl-terminal region of the GTPase-activating protein (GAP-C) and the DNA binding domain of the transcription factor ets-2, were targeted to this cell compartment. A 5-kb portion of the human c-fms proximal promoter was shown to direct expression of the transgenes to the monocytic lineage. As a result of the GAP-C transgene expression, ras-GTP levels were reduced in mature peritoneal macrophages by 70%. The terminal differentiation of monocytes was altered, as evidence by the accumulation of atypical monocytic cells in the blood. Mature peritoneal macrophages exhibited changes in colony-stimulating factor 1-dependent survival and structure. Further, expression of the colony-stimulating factor 1-stimulated gene urokinase plasminogen activator was inhibited in peritoneal macrophages. The results indicate that ras action is critical in monocytic cells after these cells have lost the capacity to traverse the cell cycle.

scholarly journals The role of phosphoinositide 3-kinase in spreading osteoclasts induced by colony-stimulating factor-1

2001 ◽  
pp. 431-440 ◽  
Author(s):  
S Palacio ◽  
R Felix
Keyword(s):  
Bone Marrow Cells ◽  
Colony Stimulating Factor ◽  
Lipid Kinase ◽  
Growth And Survival ◽  
Phosphoinositide 3 Kinase ◽  
Stimulating Factor ◽  
K Activity

BACKGROUND: Colony-stimulating factor-1 (CSF-1), a growth and survival factor for osteoclasts, stimulates these cells to spread and migrate towards a gradient of CSF-1. This may support the translocation of osteoclasts to new sites on the bone surface to be resorbed. Phosphoinositide 3-kinase (PI 3-K) is a lipid kinase participating in various signal transduction pathways. OBJECTIVE: To investigate the role of PI 3-K in the CSF-1-induced spreading of osteoclasts. METHODS: In isolated rat osteoclasts treated with or without CSF-1, the distribution of PI 3-K and proteins phosphorylated on tyrosine were investigated using immunofluorescence. In murine osteoclast-like cells grown from bone marrow cells co-cultured with osteoblasts, the activation of the PI 3-K by CSF-1 was determined both in vivo and in vitro. In vivo, the enzyme product in the cell was determined after extraction and separation with thin layer chromatography; in vitro, PI 3-K activity was measured in the pellet immunoprecipitated from the cell lysate. RESULTS: Inhibition of PI 3-K blocked the CSF-1-induced spreading of osteoclasts. In spreading osteoclasts, a portion of PI 3-K was translocated to the periphery where proteins phosphorylated on tyrosine appeared simultaneously. In osteoclast-like cells, CSF-1 stimulated PI 3-K activity. This activity could be immunoprecipitated with antibody against phophotyrosine residues. CONCLUSION: PI 3-K participates in the CSF-1-induced spreading of osteoclasts. The activated PI 3-K may induce the reorganization of the cytoskeleton resulting in spreading and migration.

scholarly journals Tumor-induced granulopoiesis unrelated to colony-stimulating factor

Blood ◽  
1983 ◽  
Vol 62 (3) ◽  
pp. 693-696
Author(s):  
H Burlington ◽  
EP Cronkite ◽  
B Heldman ◽  
N Pappas ◽  
RK Shadduck
Keyword(s):  
The Other ◽  
Mammary Adenocarcinoma ◽  
Colony Stimulating Factor ◽  
Original Tumor ◽  
Distinct Morphology ◽  
Stimulating Factor

A transplantable granulocytosis-inducing mammary adenocarcinoma of mice was used to provide evidence about the role of tumor-generated factors in granulopoiesis. The original tumor produced high levels of colony- stimulating factor (CSF) in culture as well as inhibitor to CSF. The tumor was passaged repeatedly, both in host mice and in culture, and eventually displayed a varying capacity to induce granulocytosis. Tumors that were associated with either the induction of extreme granulocytosis or near-normal granulocyte levels were selected and passaged intermittently in vivo and in culture. Two tumor lines were thus isolated: one, line C-4a, inducing granulocytosis, and the other, line 34–4H, failing to induce granulocytosis. Both lines grow at the same rate in host mice, but in culture, each displays a distinct morphology. Measurement of CSF and inhibitor produced by each line in culture showed that line 34–4H retained the capacity to produce CSF and inhibitor in spite of losing the ability to influence granulopoiesis in vivo. This suggests that the various factors shown to influence granulopoiesis in vitro may have little or no role as physiologic regulators in vivo.

scholarly journals Tumor-induced granulopoiesis unrelated to colony-stimulating factor

Blood ◽  
1983 ◽  
Vol 62 (3) ◽  
pp. 693-696 ◽  
Author(s):  
H Burlington ◽  
EP Cronkite ◽  
B Heldman ◽  
N Pappas ◽  
RK Shadduck
Keyword(s):  
The Other ◽  
Mammary Adenocarcinoma ◽  
Colony Stimulating Factor ◽  
Original Tumor ◽  
Distinct Morphology ◽  
Stimulating Factor

Abstract A transplantable granulocytosis-inducing mammary adenocarcinoma of mice was used to provide evidence about the role of tumor-generated factors in granulopoiesis. The original tumor produced high levels of colony- stimulating factor (CSF) in culture as well as inhibitor to CSF. The tumor was passaged repeatedly, both in host mice and in culture, and eventually displayed a varying capacity to induce granulocytosis. Tumors that were associated with either the induction of extreme granulocytosis or near-normal granulocyte levels were selected and passaged intermittently in vivo and in culture. Two tumor lines were thus isolated: one, line C-4a, inducing granulocytosis, and the other, line 34–4H, failing to induce granulocytosis. Both lines grow at the same rate in host mice, but in culture, each displays a distinct morphology. Measurement of CSF and inhibitor produced by each line in culture showed that line 34–4H retained the capacity to produce CSF and inhibitor in spite of losing the ability to influence granulopoiesis in vivo. This suggests that the various factors shown to influence granulopoiesis in vitro may have little or no role as physiologic regulators in vivo.

Identification of tyrosine 706 in the kinase insert as the major colony-stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the CSF-1 receptor in a murine macrophage cell line

1990 ◽  
Vol 10 (6) ◽  
pp. 2991-3002
Author(s):  
P van der Geer ◽  
T Hunter
Keyword(s):  
Cell Line ◽  
Murine Macrophage ◽  
Colony Stimulating Factor ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Major Site ◽  
Murine Macrophage Cell Line ◽  
Stimulating Factor

The receptor for colony-stimulating factor 1 (CSF-1) is a ligand-activated protein-tyrosine kinase. It has been shown previously that the CSF-1 receptor is phosphorylated on serine in vivo and that phosphorylation on tyrosine can be induced by stimulation with CSF-1. We studied the phosphorylation of the CSF-1 receptor by using the BAC1.2F5 murine macrophage cell line, which naturally expresses CSF-1 receptors. Two-dimensional tryptic phosphopeptide mapping showed that the CSF-1 receptor is phosphorylated on several different serine residues in vivo. Stimulation with CSF-1 at 37 degrees C resulted in rapid phosphorylation on tyrosine at one major site and one or two minor sites. We identified the major site as Tyr-706. The identity of Tyr-706 was confirmed by mutagenesis. This residue is located within the kinase insert domain. There was no evidence that Tyr-973 (equivalent to Tyr-969 in the human CSF-1 receptor) was phosphorylated following CSF-1 stimulation. When cells were stimulated with CSF-1 at 4 degrees C, additional phosphotyrosine-containing phosphopeptides were detected and the level of phosphorylation of the individual phosphotyrosine-containing phosphopeptides was substantially increased. In addition, we show that CSF-1 receptors are capable of autophosphorylation at six to eight major sites in vitro.

scholarly journals Interleukin-6 and the Granulocyte Colony-Stimulating Factor Receptor Are Major Independent Regulators of Granulopoiesis In Vivo But Are Not Required for Lineage Commitment or Terminal Differentiation

Blood ◽  
1997 ◽  
Vol 90 (7) ◽  
pp. 2583-2590 ◽  
Author(s):  
Fulu Liu ◽  
Jennifer Poursine-Laurent ◽  
Huai Yang Wu ◽  
Daniel C. Link
Keyword(s):  
Interleukin 6 ◽  
Terminal Differentiation ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Normal Numbers ◽  
Stimulating Factor ◽  
Deficient Mice ◽  
Additional Loss

Multiple hematopoietic cytokines can stimulate granulopoiesis; however, their relative importance in vivo and mechanisms of action remain unclear. We recently reported that granulocyte colony-stimulating factor receptor (G-CSFR)-deficient mice have a severe quantitative defect in granulopoiesis despite which phenotypically normal neutrophils were still detected. These results confirmed a role for the G-CSFR as a major regulator of granulopoiesis in vivo, but also indicated that G-CSFR independent mechanisms of granulopoiesis must exist. To explore the role of interleukin-6 (IL-6) in granulopoiesis, we generated IL-6 × G-CSFR doubly deficient mice. The additional loss of IL-6 significantly worsened the neutropenia present in young adult G-CSFR–deficient mice; moreover, exogenous IL-6 stimulated granulopoiesis in vivo in the absence of G-CSFR signals. Near normal numbers of myeloid progenitors were detected in the bone marrow of IL-6 × G-CSFR–deficient mice and their ability to terminally differentiate into mature neutrophils was observed. These results indicate that IL-6 is an independent regulator of granulopoiesis in vivo and show that neither G-CSFR or IL-6 signals are required for the commitment of multipotential progenitors to the myeloid lineage or for their terminal differentiation.

scholarly journals In vitro and in vivo effects of recombinant human granulocyte colony-stimulating factor on neutrophil functions.

1989 ◽  
Vol 35 (6) ◽  
pp. 647-652
Author(s):  
Akimichi Ohsaka ◽  
Seiichi Kitagawa ◽  
Akira Yuo ◽  
Takashi Obata ◽  
Youichi Amemiya ◽  
...  
Keyword(s):  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
In Vivo Effects ◽  
Stimulating Factor

scholarly journals A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

2009 ◽  
Vol 6 (5) ◽  
pp. 387-392 ◽  
Author(s):  
Yinan Wang ◽  
Xueling Cui ◽  
Guixiang Tai ◽  
Jingyan Ge ◽  
Nan Li ◽  
...  
Keyword(s):  
Critical Role ◽  
Peritoneal Macrophages ◽  
Activin A ◽  
Mouse Peritoneal Macrophages

Ligand-induced phosphorylation of the colony-stimulating factor 1 receptor can occur through an intermolecular reaction that triggers receptor down modulation

1990 ◽  
Vol 10 (4) ◽  
pp. 1664-1671
Author(s):  
M Ohtsuka ◽  
M F Roussel ◽  
C J Sherr ◽  
J R Downing
Keyword(s):  
Colony Stimulating Factor ◽  
Intact Cells ◽  
Atp Binding Site ◽  
Truncation Mutant ◽  
Intermolecular Mechanism ◽  
Carboxy Terminal ◽  
Lysine Substitution ◽  
Stimulating Factor

Ligand-induced tyrosine phosphorylation of the human colony-stimulating factor 1 receptor (CSF-1R) could involve either an intra- or intermolecular mechanism. We therefore examined the ability of a CSF-1R carboxy-terminal truncation mutant to phosphorylate a kinase-defective receptor, CSF-1R[met 616], that contains a methionine-for-lysine substitution at its ATP-binding site. By using an antipeptide serum that specifically reacts with epitopes deleted from the enzymatically competent truncation mutant, cross-phosphorylation of CSF-1R[met 616] on tyrosine was demonstrated, both in immune-complex kinase reactions and in intact cells stimulated with CSF-1. Both in vitro and in vivo, CSF-1R[met 616] was phosphorylated on tryptic peptides identical to those derived from wild-type CSF-1R, suggesting that receptor phosphorylation on tyrosine can proceed via an intermolecular interaction between receptor monomers. When expressed alone, CSF-1R[met 616] did not undergo ligand-induced down modulation, but its phosphorylation in cells coexpressing the kinase-active truncation mutant accelerated its degradation.

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