scholarly journals T Cell–Derived Granulocyte-Macrophage Colony-Stimulating Factor Contributes to Dry Eye Disease Pathogenesis by Promoting CD11b+ Myeloid Cell Maturation and Migration

2017 ◽  
Vol 58 (2) ◽  
pp. 1330 ◽  
Author(s):  
Thomas H. Dohlman ◽  
Julia Ding ◽  
Reza Dana ◽  
Sunil K. Chauhan
Keyword(s):  
Dry Eye ◽  
Myeloid Cell ◽  
Cell Maturation ◽  
Eye Disease ◽  
Colony Stimulating Factor ◽  
Disease Pathogenesis ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
And Migration ◽  
Stimulating Factor

scholarly journals The Human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF ) Receptor Exists as a Preformed Receptor Complex That Can Be Activated by GM-CSF, Interleukin-3, or Interleukin-5

Blood ◽  
1997 ◽  
Vol 90 (8) ◽  
pp. 3005-3017 ◽  
Author(s):  
Joanna M. Woodcock ◽  
Barbara J. McClure ◽  
Frank C. Stomski ◽  
Michael J. Elliott ◽  
Christopher J. Bagley ◽  
...  
Keyword(s):  
Myeloid Cell ◽  
Cytokine Receptor ◽  
Activation Mechanism ◽  
Receptor Complex ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The granulocyte-macrophage colony-stimulating factor (GM-CSF ) receptor is expressed on normal and malignant hematopoietic cells as well as on cells from other organs in which it transduces a variety of functions. Despite the widespread expression and pleiotropic nature of the GM-CSF receptor, little is known about its assembly and activation mechanism. Using a combination of biochemical and functional approaches, we have found that the human GM-CSF receptor exists as an inducible complex, analogous to the interleukin-3 (IL-3) receptor, and also as a preformed complex, unlike the IL-3 receptor or indeed other members of the cytokine receptor superfamily. We found that monoclonal antibodies to the GM-CSF receptor α chain (GMRα) and to the common β chain of the GM-CSF, IL-3, and IL-5 receptors (βc ) immunoprecipitated both GMRα and βc from the surface of primary myeloid cells, myeloid cell lines, and transfected cells in the absence of GM-CSF. Further association of the two chains could be induced by the addition of GM-CSF. The preformed complex required only the extracellular regions of GMRα and βc , as shown by the ability of soluble βc to associate with membrane-anchored GMRα or soluble GMRα. Kinetic experiments on eosinophils and monocytes with radiolabeled GM-CSF, IL-3, and IL-5 showed association characteristics unique to GM-CSF. Significantly, receptor phosphorylation experiments showed that not only GM-CSF but also IL-3 and IL-5 stimulated the phosphorylation of GMRα-associated βc . These results indicate a pattern of assembly of the heterodimeric GM-CSF receptor that is unique among receptors of the cytokine receptor superfamily. These results also suggest that the preformed GM-CSF receptor complex mediates the instantaneous binding of GM-CSF and is a target of phosphorylation by IL-3 and IL-5, raising the possibility that some of the biologic activities of IL-3 and IL-5 are mediated through the GM-CSF receptor complex.

scholarly journals Tumour-derived CSF2/granulocyte macrophage colony stimulating factor controls myeloid cell accumulation and progression of gliomas

2020 ◽  
Vol 123 (3) ◽  
pp. 438-448 ◽  
Author(s):  
Malgorzata Sielska ◽  
Piotr Przanowski ◽  
Maria Pasierbińska ◽  
Kamil Wojnicki ◽  
Katarzyna Poleszak ◽  
...  
Keyword(s):  
Myeloid Cell ◽  
Colony Stimulating Factor ◽  
Cell Accumulation ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals M-CSF and GM-CSF Regulation of STAT5 Activation and DNA Binding in Myeloid Cell Differentiation is Disrupted in Nonobese Diabetic Mice

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
B. Rumore-Maton ◽  
J. Elf ◽  
N. Belkin ◽  
B. Stutevoss ◽  
F. Seydel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
Myeloid Cell ◽  
Mouse Bone Marrow ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Nonobese Diabetic ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Defects in macrophage colony-stimulating factor (M-CSF) signaling disrupt myeloid cell differentiation in nonobese diabetic (NOD) mice, blocking myeloid maturation into tolerogenic antigen-presenting cells (APCs). In the absence of M-CSF signaling, NOD myeloid cells have abnormally high granulocyte macrophage colony-stimulating factor (GM-CSF) expression, and as a result, persistent activation of signal transducer/activator of transcription 5 (STAT5). Persistent STAT5 phosphorylation found in NOD macrophages is not affected by inhibiting GM-CSF. However, STAT5 phosphorylation in NOD bone marrow cells is diminished if GM-CSF signaling is blocked. Moreover, if M-CSF signaling is inhibited, GM-CSF stimulationin vitrocan promote STAT5 phosphorylation in nonautoimmune C57BL/6 mouse bone marrow cultures to levels seen in the NOD. These findings suggest that excessive GM-CSF production in the NOD bone marrow may interfere with the temporal sequence of GM-CSF and M-CSF signaling needed to mediate normal STAT5 function in myeloid cell differentiation gene regulation.

Human Interleukin-3/Granulocyte Macrophage-Colony Stimulating Factor Knock-In Mice Support Human Myeloid Cell Reconstitution and Human Immune Responses In the Lung.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3789-3789
Author(s):  
Tim Willinger ◽  
Anthony Rongvaux ◽  
Hitoshi Takizawa ◽  
Elizabeth E. Eynon ◽  
Sean Stevens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Myeloid Cell ◽  
Humanized Mice ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Human Immune ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Abstract 3789 Humanized mice, i.e. mice with a functional human immune system, have great potential to study human immunology in vivo and to allow vaccine testing. To this end, mice need to fully support engraftment with human immune cells, allow infection with human pathogens, and mount effective human immune responses to pathogens. A major limitation of current humanized mice is the poor development and function of human myeloid cells. Here we report a novel strategy to overcome this limitation by generating human interleukin-3/granulocyte macrophage colony stimulating factor knock-in (hIL-3/GM-CSF KI) mice to create a better environment for human myeloid cells. These mice faithfully expressed human GM-CSF and IL-3 and developed pulmonary alveolar proteinosis (PAP) due to elimination of mouse GM-CSF. We demonstrate that hIL-3/GM-CSF KI mice engrafted with human CD34+ hematopoietic cells had improved human myeloid cell reconstitution in the lung. In particular, hIL-3/GM-CSF KI mice supported the development of human alveolar macrophages that partially rescued the PAP syndrome. In addition, these mice showed an enhanced systemic inflammatory response to LPS. Finally, humanization of IL-3 and GM-CSF lead to a stronger innate immune response against influenza virus infection. In summary, hIL-3/GM-CSF KI mice represent a new mouse model to study human immune responses in the lung and against pathogens such as influenza. Disclosures: Stevens: Regeneron Pharmaceuticals: Employment; AnaptysBio Inc: Employment.

scholarly journals Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce rapid phosphorylation and activation of the proto-oncogene Raf-1 in a human factor-dependent myeloid cell line

Blood ◽  
1991 ◽  
Vol 77 (2) ◽  
pp. 243-248 ◽  
Author(s):  
Y Kanakura ◽  
B Druker ◽  
KW Wood ◽  
HJ Mamon ◽  
K Okuda ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Line ◽  
Human Factor ◽  
Myeloid Cell ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Myeloid Cell Line ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The product of the c-raf-1 proto-oncogene, Raf-1, is a 74,000-dalton cytoplasmic serine/threonine protein kinase that has been implicated as an intermediate in signal transduction mechanisms. In the human factor- dependent myeloid cell line MO7, both granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3) were found to induce rapid, dose-dependent phosphorylation of Raf-1, which resulted in altered Raf-1 mobility in sodium dodecyl sulfate-polyacrylamide gels. The increase in phosphorylation was due primarily to an increase in phosphoserine, with only a minor component (less than 2%) of phosphotyrosine. PMA (12-phorbol 13-myristic acid) also induced Raf-1 phosphorylation in MO7 cells, but the resulting alteration in electrophoretic mobility was different than that observed after GM-CSF or IL-3. GM-CSF and IL-3 rapidly and transiently increased Raf-1 kinase activity using Histone H1 as a substrate in an immune complex kinase assay in vitro. These results suggest that phosphorylation of Raf-1 could play a role in some aspect of GM-CSF and IL-3 signal transduction.

scholarly journals Macrophage colony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts.

1993 ◽  
Vol 178 (5) ◽  
pp. 1733-1744 ◽  
Author(s):  
K Fuller ◽  
J M Owens ◽  
C J Jagger ◽  
A Wilson ◽  
R Moss ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Osteoclast Formation ◽  
Cell Polarization ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
And Migration ◽  
Established Role ◽  
Stimulating Factor

Macrophage colony-stimulating factor (M-CSF) is known to play an important role in osteoclast formation. However, its actions on mature cells have not been fully characterized. We now report that M-CSF dramatically stimulates osteoclastic motility and spreading; osteoclasts responded to a gradient of M-CSF with orientation, and random cell polarization occurred after isotropic exposure. M-CSF also supported the survival of osteoclasts by preventing apoptosis. Paradoxically, M-CSF inhibits bone resorption by isolated osteoclasts. We found that this was effected predominantly by reduction in the number of excavations. Thus, M-CSF showed a propensity to suppress resorption through a reduction in the proportion of cells that were resorbing bone. Our data suggest that apart from the established role of M-CSF in the provision of precursors for osteoclastic induction, a major role for M-CSF in bone resorption is to enhance osteoclastic survival, migration, and chemotaxis. It seems appropriate that during these processes resorptive functions should be suppressed. We suggest that M-CSF continues to modulate osteoclastic activity once osteoclasts are on resorptive sites, through regulation of the balance between resorption and migration, such that not only the quantity, but the spatial pattern of resorption can be controlled by adjacent M-CSF-secreting cells of osteoblastic lineage.

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