The Critical Role of the Colony-Stimulating Factor-1 Receptor in the Differentiation of Myeloblastic Leukemia Cells

Hamilton, John A.; Whitty, Genevieve; Masendycz, Paul; Wilson, Nicholas J.; Jackson, Jacob T.; Nardo, Dominic De; Scholz, Glen M.

doi:10.1158/1541-7786.mcr-07-0361

Cited by 7 publications

(3 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CSF1R inhibition not only leads to microglial demise but also other CSF1R-expressing cells both in vitro and in vivo (Elmore et al, 2014 ). Moreover, CSF1R is involved in inflammation-mediated activation by macrophages (Pixley and Stanley, 2004 ; Hamilton et al, 2008 ; Hamilton, 2008 ). CSF1R inhibitors such as PLX3397, BLZ945 and GW2580 have been administered orally to manipulate microglia in the CNS (for review see, Wieghofer et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

CSF1R Inhibition Reduces Microglia Proliferation, Promotes Tissue Preservation and Improves Motor Recovery After Spinal Cord Injury

Gerber

Saint-Martin

Bringuier

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by activation and proliferation of resident microglia as well as infiltrating peripheral monocyte-derived macrophages. Depending on the time post-lesion, positive and detrimental influences of microglia/macrophages on axonal regeneration had been reported after SCI, raising the issue whether their modulation may represent an attractive therapeutic strategy. Colony-stimulating factor 1 (CSF1) regulates microglia/macrophages proliferation, differentiation and survival thus, pharmacological treatments using CSF1 receptor (CSF1R) inhibitors had been used to ablate microglia. We analyzed the effect of chronic (10 weeks) food diet containing GW2580 (a CSF1R inhibitor) in mice that underwent lateral spinal cord hemisection (HS) at vertebral thoracic level 9. Treatment started 4 weeks prior to SCI and continued until 6 weeks post-lesion. We first demonstrate that GW2580 treatment did not modify microglial response in non-injured spinal cords. Conversely, a strong decrease in proliferating microglia was observed following SCI. Second, we showed that GW2580 treatment improved some parameters of motor recovery in injured animals through better paw placement. Using in and ex vivo magnetic resonance imaging (MRI), we then established that GW2580 treatment had no effect on lesion extension and volume. However, histological analyses revealed that GW2580-treated animals had reduced gliosis and microcavity formation following SCI. In conclusion, CSF1R blockade using GW2580 specifically inhibits SCI-induced microglia/macrophages proliferation, reduces gliosis and microcavity formations and improves fine motor recovery after incomplete SCI. Preventing microglial proliferation may offer therapeutic approach to limit neuroinflammation, promote tissue preservation and motor recovery following SCI.

show abstract

Section: Introductionmentioning

confidence: 99%

CSF1R Inhibition Reduces Microglia Proliferation, Promotes Tissue Preservation and Improves Motor Recovery After Spinal Cord Injury

Gerber

Saint-Martin

Bringuier

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…1 CSF-1 may be sufficient in physiologic conditions to generate macrophages with a M2 phenotype, which are involved in debris scavenging, angiogenesis, tissue remodeling, and wound healing, whereas M1 macrophages with an inflammatory phenotype could be produced independently of CSF-1 under stimulation with granulocyte-macrophage colony-stimulating factor, interferon ␥, or microbial products. 2 Mice lacking active CSF-1 production as the result of a null mutation in coding region of the CSF-1 gene, known as op/op osteopetrotic mice, demonstrate severe deficiency of macrophages 3 that is restored by the injection of CSF-1 in several tissues. 4 The biologic effects of CSF-1 are mediated by a unique receptor, CSF-1R, which is encoded by the c-fms protooncogene.…”

Section: Introductionmentioning

confidence: 99%

Colony-stimulating factor-1–induced oscillations in phosphatidylinositol-3 kinase/AKT are required for caspase activation in monocytes undergoing differentiation into macrophages

Jacquel

Benikhlef

Paggetti

et al. 2009

Blood

View full text Add to dashboard Cite

The differentiation of human peripheral blood monocytes into resident macrophages is driven by colony-stimulating factor-1 (CSF-1), which upon interaction with CSF-1 receptor (CSF-1R) induces within minutes the phosphorylation of its cytoplasmic tyrosine residues and the activation of multiple signaling complexes. Caspase-8 and -3 are activated at day 2 to 3 and contribute to macrophage differentiation, for example, through cleavage of nucleophosmin. Here, we show that the phosphatidylinositol-

show abstract

“…only proliferative microglia) that is inhibited by GW2580 [21,22]. CSF1R is principally expressed by microglia in the intact CNS [45][46][47]. Therefore, we cannot exclude that GW2580 treatment may likewise have off-target effects and could affect neurons that also express CSF1R [48] or infiltrating macrophages [for review see [15]].…”

Section: Discussionmentioning

confidence: 99%

Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates

Poulen

Aloy

Bringuier

et al. 2021

Preprint

View full text Add to dashboard Cite

No curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery. In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia, we thus used an oral administration of GW2580, a CSF1R inhibitor. First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissues preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity. Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves functional motor function recovery, and promotes tissue protection. Notably, three months after lesion microglia reactivity returned to baseline value. Finally, to initiate the investigation on molecular mechanisms induced by a transient post-SCI GW2580-treatment, we used microglia-specific transcriptomic analysis in mice. Notably, we detected a downregulation in the expression of inflammatory-associated genes and we identified genes that were up-regulated by SCI and further downregulated by the treatment. Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation.

show abstract

The Critical Role of the Colony-Stimulating Factor-1 Receptor in the Differentiation of Myeloblastic Leukemia Cells

Abstract: How diverse stimuli control hemopoietic lineage development is unknown. An early event during induction of macrophage differentiation in the myeloblastic leukemia M1 cell line by different stimuli, such as leukemia inhibitory factor (LIF) and interleukin-6

Cited by 7 publications

References 43 publications

CSF1R Inhibition Reduces Microglia Proliferation, Promotes Tissue Preservation and Improves Motor Recovery After Spinal Cord Injury

CSF1R Inhibition Reduces Microglia Proliferation, Promotes Tissue Preservation and Improves Motor Recovery After Spinal Cord Injury

Colony-stimulating factor-1–induced oscillations in phosphatidylinositol-3 kinase/AKT are required for caspase activation in monocytes undergoing differentiation into macrophages

Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates

Contact Info

Product

Resources

About