Role and Expression of Colony Stimulating Factor-1 and Steel Factor Receptors and their Ligands during Pregnancy in the Mouse

1992 ◽  
Vol 4 (6) ◽  
pp. 619 ◽  
Author(s):  
RJ Arceci ◽  
S Pampfer ◽  
JW Pollard
Keyword(s):  
Growth Factors ◽  
Preimplantation Embryo ◽  
Sex Steroid ◽  
Colony Stimulating Factor ◽  
Sex Steroid Hormone ◽  
Steel Factor ◽  
Embryonic Tissues ◽  
Polypeptide Growth Factors ◽  
Paracrine Action ◽  
Stimulating Factor

It is becoming apparent that the effects of female sex steroid hormones can be mediated by locally synthesized polypeptide growth factors in the uterus. In this paper we describe the patterns of expression of two such growth factors, steel factor and colony stimulating factor-1 (CSF-I), and their transmembrane tyrosine kinase receptors, the products of the c-kit and c-fms proto-oncogenes respectively. Both these uterine synthesized cytokines are directed to uterine hematopoietic cells, the preimplantation embryo and to the extra-embryonic tissues during the postimplantation period. Studies with the CSF-1-deficient osteopetrotic (op/op) mouse show that CSF-1 has important roles during embryonic development and in the regulation of uterine macrophages. These studies establish that CSF-1, whose sex steroid hormone-induced synthesis is restricted to the uterine epithelium, has a paracrine action on embryos as well as being a mediator of epithelial-mesenchymal interactions.

scholarly journals Aberrant expression of proatherogenic cytokines and growth factors in human umbilical vein endothelial cells from newborns of type 2 diabetic women

2021 ◽  
Vol 9 ◽  
pp. 205031212110268
Author(s):  
Samar Sultan
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Cells ◽  
Growth Factors ◽  
Umbilical Vein ◽  
Colony Stimulating Factor ◽  
Human Umbilical Vein ◽  
Normal Glucose ◽  
Umbilical Vein Endothelial Cells ◽  
Stimulating Factor

Objectives: This study reports the levels of cytokines, chemokines, and growth factors previously identified as taking part in the pathology of atherosclerosis in human umbilical vein endothelial cells derived from mothers with type 2 diabetes and compares them with those in human umbilical vein endothelial cells derived from healthy mothers under normal glucose conditions. Methods: Cytokine analysis measures of human umbilical vein endothelial cell lysates were obtained using a multiple analyte profiling (xMAP) assay based on magnetic bead-based technology, using the MAGPIX instrument. The correlation between cytokines, chemokines, and growth factors was examined statistically in human umbilical vein endothelial cells derived from mothers with type 2 diabetes. Results: This study showed that the expression of proinflammatory cytokine interleukin-1 alpha was significantly greater in human umbilical vein endothelial cells derived from mothers with type 2 diabetes than those derived from healthy mothers. The protein level of granulocyte colony-stimulating factor was higher in human umbilical vein endothelial cells derived from mothers with type 2 diabetes than those derived from healthy mothers. A significant positive correlation was demonstrated between the protein expression of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in human umbilical vein endothelial cells derived from mothers with type 2 diabetes. Conclusion: Diabetes evokes a persistent inflammatory phenotype in human umbilical vein endothelial cells, as indicated by the enhanced production of cytokines and growth factors under normal glucose conditions.

scholarly journals Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Dose Intensification With Granulocyte Colony-Stimulating Factor Markedly Depletes Stem Cell Reserve for Autologous Bone Marrow Transplantation

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4996-5001 ◽  
Author(s):  
Arnold Freedman ◽  
Donna Neuberg ◽  
Peter Mauch ◽  
John Gribben ◽  
Robert Soiffer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Standard Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Dose Intensification ◽  
Sequential Trials ◽  
Stimulating Factor

Abstract Hematopoietic growth factors allow dose escalation of chemotherapy. This approach may potentially reduce the quality and quantity of hematopoietic stem cells. The capacity of stem cells recovered after dose intensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hematopoietic engraftment was compared in two sequential trials of induction therapy (standard dose cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] without growth factors or dose intensification CHOP supported by granulocyte colony-stimulating factor [G-CSF ]) followed by identical myeloablative therapy and autologous stem cell support. Neutrophil, platelet, and red blood cell (RBC) engraftment were compared on days 100, 180, and 360 after stem cell reinfusion. Despite similar patient characteristics including reinfusion of comparable numbers of marrow mononuclear cells, after stem cell transplantation, a highly significant prolongation of neutrophil and platelet engraftment was seen in patients who received high dose CHOP and G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemotherapy and G-CSF recruited stem cells into a proliferative phase and that G-CSF allowed retreatment at a time when stem cells were susceptible to damage by cytotoxic therapy. Such inadequate hematologic engraftment after myeloablative therapy might be avoided by either shortening the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additional stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be used with caution if stem cells are to be used to support myeloablative therapy.

scholarly journals Differential and synergistic effects of human granulocyte-macrophage colony-stimulating factor and human granulocyte colony-stimulating factor on hematopoiesis in human long-term marrow cultures

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 493-499 ◽  
Author(s):  
DE Hogge ◽  
JD Cashman ◽  
RK Humphries ◽  
CJ Eaves
Keyword(s):  
Growth Factors ◽  
Synergistic Effects ◽  
S Phase ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Single Addition ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The ability of granulocyte-macrophage colony-stimulating factor (GM- CSF) and G-CSF to influence hematopoiesis in long-term cultures (LTC) of human marrow was studied by cocultivating light density normal human marrow cells with human marrow fibroblast feeders engineered by retroviral infection to constitutively produce one of these growth factors. Feeders producing stable levels of 4 ng/mL GM-CSF or 20 ng/mL G-CSF doubled the output of mature nonadherent cells. The numbers of both colony forming unit-GM (CFU-GM) and erythroid burst forming unit (BFU-E) in the G-CSF LTC were also increased (twofold and fourfold, respectively, after 5 weeks in culture), but this effect was not seen with the GM-CSF feeders. At the time of the weekly half medium change 3H-thymidine suicide assays showed primitive adherent layer progenitors in LTC to be quiescent in both the control and GM-CSF cultures. In contrast, in the G-CSF cultures, a high proportion of primitive progenitors were in S-phase. A single addition of either recombinant GM- CSF or G-CSF to LTC in doses as high as 80 ng/mL and 150 ng/mL, respectively, failed to induce primitive progenitor cycling. However, three sequential daily additions of 150 ng/mL G-CSF did stimulate primitive progenitors to enter S-phase and a single addition of 5 or 12.5 ng/mL of G-CSF together with 10 ng/mL GM-CSF was able to elicit the same effect. Thus, selective elevation of G-CSF in human LTC stimulates proliferation of primitive clonogenic progenitors, which may then proceed through to the terminal stages of granulopoiesis. In contrast, the effects of GM-CSF in this system appear limited to terminally differentiating granulopoietic cells. However, when both GM- CSF and G-CSF are provided together, otherwise biologically inactive doses show strong stimulatory activity. These findings suggest that the production of both of these growth factors by normal stromal cells may contribute to the support and proliferation of hematopoietic cells, not only in LTC, but also in the microenvironment of the marrow in vivo.

scholarly journals Murine myeloid cells transformed by myb require fibroblast-derived or autocrine growth factors in addition to granulocyte-macrophage colony- stimulating factor for proliferation

Blood ◽  
1994 ◽  
Vol 83 (1) ◽  
pp. 209-216 ◽  
Author(s):  
EM Macmillan ◽  
TJ Gonda
Keyword(s):  
Growth Factors ◽  
Myeloid Cells ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Autocrine Growth ◽  
Gm Csf ◽  
Absolute Dependence ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Murine myeloid cells can be transformed in vitro by infection with recombinant retroviruses carrying activated myb genes. While these myb- transformed hematopoietic cells (MTHCs) can proliferate continuously in culture, they exhibit several characteristics of progenitor cells of the granulocyte-macrophage (GM) lineage, including an absolute dependence on hematopoietic growth factors (HGFs) such as GM colony- stimulating factor (GM-CSF) for survival and growth. Whereas we have previously shown that MTHCs respond synergistically to certain combinations of HGFs, we report here that MTHCs apparently require two HGFs for proliferation, because GM-CSF alone appears insufficient to promote growth when MTHCs are cultured at very low densities. However, proliferation can be stimulated by either increasing the density at which MTHCs are cultured (implying the production of an autocrine growth factor) or by the presence of a feeder layer of irradiated fibroblasts. We find that the activity of such feeder layers is greatest when the MTHCs are allowed to contact them directly; and by using mutant fibroblast lines, that it depends on the production of CSF- 1, but not Steel factor (SLF). In contrast, the autocrine factor appears not to be either CSF-1 or SLF, and the possibility is raised that it may represent a novel HGF activity. Potential implications of these results for normal and leukemic hematopoiesis are discussed.

scholarly journals Granulocyte-macrophage colony-stimulating factor, interleukin-3, and steel factor induce rapid tyrosine phosphorylation of p42 and p44 MAP kinase

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2880-2887 ◽  
Author(s):  
K Okuda ◽  
JS Sanghera ◽  
SL Pelech ◽  
Y Kanakura ◽  
M Hallek ◽  
...  
Keyword(s):  
Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Colony Stimulating Factor ◽  
Steel Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Tyrosyl Phosphorylation ◽  
Stimulating Factor

Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF), Interleukin- 3 (IL-3), and Steel Factor (SF) induce proliferation of hematopoietic cells through binding to specific, high-affinity, cell surface receptors. However, little is known about postreceptor signal transduction pathways. In previous studies, we noted that each of these three factors could independently support proliferation of the human MO7 cell line, and also that each factor induced a rapid increase in protein-tyrosyl phosphorylation. Although the proteins phosphorylated on tyrosine by GM-CSF and IL-3 are similar or identical in MO7 cells, many of the proteins that are phosphorylated on tyrosine after SF are different. However, two proteins, p42 and p44, were prominently phosphorylated in response to all three of the factors. In MO7 cells, the tyrosyl phosphorylation of p42 and p44 was transient, peaking at 5 to 15 minutes. In contrast to many of the other proteins which are tyrosyl phosphorylated in response to these factors, phosphorylation of p42 and p44 was temperature-dependent, occurring at 37 degrees C, but not at 4 degrees C. We identified the p42 protein as p42 Mitogen- Activated Protein Kinase (p42mapk, ERK-2) and the p44 as a p42mapk- related protein using monospecific antisera to MAP kinase. GM-CSF, IL- 3, and SF were each found to induce MAP kinase activity when assayed in vitro using myelin basic protein (MBP) as a substrate. Remarkably, we found that GM-CSF-induced tyrosyl phosphorylation of p42 and p44 even in nonproliferative cells (neutrophils) that respond to this CSF, and that p42 and p44 were two of the most prominently tyrosyl phosphorylated proteins following GM-CSF stimulation of these cells. These results implicate p42mapk and p44 as important signal transducing molecules in myeloid cells, and it is likely that these kinases play a role as part of a sequential “kinase cascade” linking growth factor receptors to mitogenesis and other cellular responses.

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