Granulocyte-colony stimulating factor (G-CSF) alters the cytokine-pattern in human T-cells in vivo

1998 ◽  
Vol 16 ◽  
pp. S184
Author(s):  
T Schultewolter ◽  
HD Ottinger ◽  
DW Beelen ◽  
SN Wagner ◽  
UW Schaefer ◽  
...  
Keyword(s):  
T Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cytokine Pattern ◽  
Human T Cells ◽  
Stimulating Factor ◽  
Factor G

scholarly journals Modulation of Neutrophil‐Mediated Activity Against the Pseudohyphal Form ofCandida albicansby Granulocyte Colony‐Stimulating Factor (G‐CSF) Administered In Vivo

1999 ◽  
Vol 179 (5) ◽  
pp. 1301-1304 ◽  
Author(s):  
J. Milton Gaviria ◽  
Jo‐Anne H. van Burik ◽  
David C. Dale ◽  
Richard K. Root ◽  
W. Conrad Liles
Keyword(s):  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Factor G

Effects of Granulocyte Colony Stimulating Factor (G-CSF) On Monosomy 7 Aneuploidy and T Cell Subsets in Healthy Donors.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3147-3147
Author(s):  
Matthew J. Olnes ◽  
Susan Leitman ◽  
Angelique Biancotto ◽  
J. Philip McCoy ◽  
Susan Miranda ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chromosomal Abnormalities ◽  
T Cell Subsets ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Monosomy 7 ◽  
Healthy Donors ◽  
Stimulating Factor ◽  
Factor G

Abstract Abstract 3147 Poster Board III-84 Recent reports of chromosomal and immunological abnormalities in healthy donors receiving granulocyte colony stimulating factor (G-CSF) have raised concerns among hematologists that this popular cytokine may promote genomic instability or alter immune surveillance (Pampilon D et al Transfusion 2008; 48(7):1495-501). We previously reported that G-CSF altered the Th1:Th2 ratio in healthy individuals following short-term administration (Blood 2000 Apr 1;95(7):2269-74), but reported no new karyotypic abnormities after in vitro culture of bone marrow mononuclear cells with pharmacological doses of G-CSF (Proc Natl Acad Sci 2006 Sep 26;103(39):14483-8). There is no systematic study of the long-term effects of administering granulocyte colony stimulating factor (G-CSF) to healthy individuals. We examined CD34 cells of 10 healthy stem cell donors after they had received 10 mcg/kg G-CSF for 4 days; fluorescent in situ hybridization (FISH) was the method employed to monitor chromosomal changes. We also studied 37 healthy granulocyte donors who received G-CSF (5ug/Kg x 1 day) and dexamethosone for up to 42 times (median= 15; range 6-42) using FISH to examine chromosomes 7 and 8 and flow cytometry to define their T cell subsets. FISH did not detect chromosomal abnormalities in the CD34 cells of 10 donors mobilized with G-CSF; neither could monosomy 7 cells be isolated after culturing cells in media with 400 ng/mL G-CSF (previously shown to support outgrowth of monosomy 7 cells) for two weeks. Furthermore, FISH did not detect aneuploidy in the 37 regular granulocyte donors. Evaluation of T cell subsets by flow cytometry demonstrated similar percentages of CD4+ T cells in 18 granulocyte donors as compared to 23 untreated controls (57.5% vs 56.5%). However, donors had increased numbers of CD4+TNFαa+ Th1 T cells and decreased CD4+IL-6+ Th2 T cells (4.2% vs 1.6%, P= 0.0003 and 11% vs. 35%, P=0.04 respectively), while the donor Th2 subset expressed significantly more IL-6 per cell (P<0.01). CD4+CD25+FoxP3+ regulatory T cells (Tregs) were significantly increased in G-CSF-treated donors (10.1% vs 6.0%, P<0.0001), while Th17 T cells were not significantly different (2.4% vs 0.7%, P=0.423). G-CSF does not produce chromosomal abnormalities of monosomy 7 or trisomy 8 in healthy SCT donors or in serially treated granulocyte donors. However, there are significant changes in T cell subsets that modulate the immune response. Disclosures No relevant conflicts of interest to declare.

scholarly journals Granulocyte-colony–stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis

2017 ◽  
Vol 114 (42) ◽  
pp. 11235-11240 ◽  
Author(s):  
Lilian Basso ◽  
Tamia K. Lapointe ◽  
Mircea Iftinca ◽  
Candace Marsters ◽  
Morley D. Hollenberg ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Visceral Pain ◽  
Inflammatory Diseases ◽  
Intrathecal Injection ◽  
Cathepsin S ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Factor G

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony–stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF–induced visceral pain in vivo. Finally, administration of G-CSF–neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron–microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.

Human Granulocyte Colony-Stimulating Factor (G-CSF) Stimulates the In Vitro and In Vivo Development But Not Commitment of Primitive Multipotential Progenitors From Transgenic Mice Expressing the Human G-CSF Receptor

Blood ◽  
1998 ◽  
Vol 92 (12) ◽  
pp. 4632-4640 ◽  
Author(s):  
Feng-Chun Yang ◽  
Sumiko Watanabe ◽  
Kohichiro Tsuji ◽  
Ming-jiang Xu ◽  
Azusa Kaneko ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blast Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitors ◽  
Clonal Cultures ◽  
Stimulating Factor ◽  
Factor G

Granulocyte colony-stimulating factor (G-CSF) stimulates the proliferation and restricted differentiation of hematopoietic progenitors into neutrophils. To clarify the effects of G-CSF on hematopoietic progenitors, we generated transgenic (Tg) mice that had ubiquitous expression of the human G-CSF receptor (hG-CSFR). In clonal cultures of bone marrow and spleen cells obtained from these mice, hG-CSF supported the growth of myelocytic as well as megakaryocytic, mast cell, mixed, and blast cell colonies. Single-cell cultures of lineage-negative (Lin−)c-Kit+Sca-1+ or Sca-1− cells obtained from the Tg mice confirmed the direct effects of hG-CSF on the proliferation and differentiation of various progenitors. hG-CSF also had stimulatory effects on the formation of blast cell colonies in cultures using 5-fluorouracil–resistant hematopoietic progenitors and clone-sorted Lin−c-Kit+Sca-1+ primitive hematopoietic cells. These colonies contained different progenitors in proportions similar to those obtained when mouse interleukin-3 was used in place of hG-CSF. Administration of hG-CSF to Tg mice led to significant increases in spleen colony-forming and mixed/blast cell colony-forming cells in bone marrow and spleen, but did not alter the proportion of myeloid progenitors in total clonogenic cells. These results show that, when functional G-CSFR is present on the cell surface, hG-CSF stimulates the development of primitive multipotential progenitors both in vitro and in vivo, but does not induce exclusive commitment to the myeloid lineage.

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