Regulation and function of macrophage colony-stimulating factor (CSF1) in the chicken immune system

Z, Wu; Harne, Rakhi; Chintoan-Uta, Cosmin; Hu, Tuanjun; Wallace, Robert; MacCallum, Amanda; Stevens, Mark P.; Kaiser, Pete; Balic, Adam; Hume, David

doi:10.1016/j.dci.2019.103586

Cited by 25 publications

(23 citation statements)

References 52 publications

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“…The intranasal administration of rh-CSF1 further enhanced the elevation of CSF1 and CSF1R on neurons and astrocytes, leading to improved short-term neurological outcomes with significantly less infarction volumes, neuronal degeneration, and apoptosis. Our findings echoed other studies showing that CSF1 reduced neuronal damage after stroke, experimental autoimmune encephalomyelitis, and AD [ 16 , 21 , 22 ]. Neurons were more vulnerable to ischemia and chemical damage in CSF1-deficient mice [ 58 ].…”

Section: Discussionsupporting

confidence: 90%

“…CSF1 is a single-pass type I membrane cytokine and has an essential role in regulating the survival, proliferation, and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes [ 16 , 47 ]. In the CNS, CSF1 contributes to the proliferation and differentiation of microglia and is critical to microglia development [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…CSF1 is produced by a variety of cell types, including monocytes/macrophages, endothelial cells, fibroblasts, and bone marrow stromal cells [ 15 ]. CSF1 primarily regulates the proliferation, differentiation, and survival of mononuclear phagocytic systems (e.g., bone marrow progenitors, circulating monocytes, and tissue macrophages) [ 16 ], which are mediated by the protein tyrosine kinase receptor, CSF1R [ 17 ]. In the central nervous system (CNS), CSF1 is widely expressed in neurons, microglia, astrocytes, and oligodendrocytes [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE

Xiao

Liu

Doycheva

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress (OS) and neuronal apoptosis are major pathological processes after hypoxic-ischemic encephalopathy (HIE). Colony stimulating factor 1 (CSF1), binding to CSF1 receptor (CSF1R), has been shown to reduce neuronal loss after hypoxic-ischemia- (HI-) induced brain injury. In the present study, we hypothesized that CSF1 could alleviate OS-induced neuronal degeneration and apoptosis through the CSF1R/PLCG2/PKA/UCP2 signaling pathway in a rat model of HI. A total of 127 ten-day old Sprague Dawley rat pups were used. HI was induced by right common carotid artery ligation with subsequent exposure to hypoxia for 2.5 h. Exogenous recombinant human CSF1 (rh-CSF1) was administered intranasally at 1 h and 24 h after HI. The CSF1R inhibitor, BLZ945, or phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, was injected intraperitoneally at 1 h before HI induction. Brain infarct volume measurement, cliff avoidance test, righting reflex test, double immunofluorescence staining, western blot assessment, 8-OHdG and MitoSOX staining, Fluoro-Jade C staining, and TUNEL staining were used. Our results indicated that the expressions of endogenous CSF1, CSF1R, p-CSF1R, p-PLCG2, p-PKA, and uncoupling protein2 (UCP2) were increased after HI. CSF1 and CSF1R were expressed in neurons and astrocytes. Rh-CSF1 treatment significantly attenuated neurological deficits, infarct volume, OS, neuronal apoptosis, and degeneration at 48 h after HI. Moreover, activation of CSF1R by rh-CSF1 significantly increased the brain tissue expressions of p-PLCG2, p-PKA, UCP2, and Bcl2/Bax ratio, but reduced the expression of cleaved caspase-3. The neuroprotective effects of rh-CSF1 were abolished by BLZ945 or U73122. These results suggested that rh-CSF1 treatment attenuated OS-induced neuronal degeneration and apoptosis after HI, at least in part, through the CSF1R/PLCG2/PKA/UCP2 signaling pathway. Rh-CSF1 may serve as therapeutic strategy against brain damage in patients with HIE.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE

Xiao

Liu

Doycheva

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Colony-stimulating factor 1 (CSF1), also known as macrophage-CSF (M-CSF), is a secreted cytokine that is essential to regulate the growth and differentiation of macrophage lineage cells (e.g., macrophages, osteoclasts, and microglia) [7,8]. In the central nervous system (CNS), CSF1 is primarily expressed on neurons, microglia, astrocytes, and oligodendrocytes [7,9], which can regulate neuroinflammation, reconstruct damaged white matter, and maintain social behavior [10,11].…”

Section: Introductionmentioning

confidence: 99%

Rh-CSF1 attenuates neuroinflammation via the CSF1R/PLCG2/PKCε pathway in a rat model of neonatal HIE

Xiao

Liu

Doycheva

et al. 2020

J Neuroinflammation

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Background: Hypoxic-ischemic encephalopathy (HIE) is a life-threatening cerebrovascular disease. Neuroinflammation plays an important role in the pathogenesis of HIE, in which microglia are key cellular mediators in the regulation of neuroinflammatory processes. Colony-stimulating factor 1 (CSF1), a specific endogenous ligand of CSF1 receptor (CSF1R), is crucial in microglial growth, differentiation, and proliferation. Recent studies showed that the activation of CSF1R with CSF1 exerted anti-inflammatory effects in a variety of nervous system diseases. This study aimed to investigate the anti-inflammatory effects of recombinant human CSF1 (rh-CSF1) and the underlying mechanisms in a rat model of HIE. Methods: A total of 202 10-day old Sprague Dawley rat pups were used. HI was induced by the right common carotid artery ligation with subsequent exposure of 2.5-h hypoxia. At 1 h and 24 h after HI induction, exogenous rh-CSF1 was administered intranasally. To explore the underlying mechanism, CSF1R inhibitor, BLZ945, and phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, were injected intraperitoneally at 1 h before HI induction, respectively. Brain infarct area, brain water content, neurobehavioral tests, western blot, and immunofluorescence staining were performed. Results: The expressions of endogenous CSF1, CSF1R, PLCG2, protein kinase C epsilon type (PKCε), and cAMP response element-binding protein (CREB) were gradually increased after HIE. Rh-CSF1 significantly improved the neurological deficits at 48 h and 4 weeks after HI, which was accompanied by a reduction in the brain infarct area, brain edema, brain atrophy, and neuroinflammation. Moreover, activation of CSF1R by rh-CSF1 significantly increased the expressions of p-PLCG2, p-PKCε, and p-CREB, but inhibited the activation of neutrophil infiltration, and downregulated the expressions of IL-1β and TNF-α. Inhibition of CSF1R and PLCG2 abolished these neuroprotective effects of rh-CSF1 after HI.

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“…An interesting alternative for depleting macrophages, however, is the use of antibodies to block the action of macrophage colony stimulating factor (CSF1), a growth factor that promotes the differentiation and survival of macrophages [ 37 , 38 ]. This antibody has long been available for mice but an antibody that specifically targets and depletes chicken CSF1 was developed only recently [ 39 ]. The two methods differ in their mechanism, as anti-CSF1 antibodies block the differentiation of macrophages early on, while clodronate liposomes target phagocytising macrophages.…”

Section: Discussionmentioning

confidence: 99%

Depletion of Embryonic Macrophages Leads to a Reduction in Angiogenesis in the Ex Ovo Chick Chorioallantoic Membrane Assay

Tay

Cheyne

Demeyere

et al. 2020

Cells

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Macrophages play an important but poorly understood role in angiogenesis. To investigate their role in vessel formation, relevant in vivo models are crucial. Although the chick chorioallantoic membrane (CAM) model has been frequently used as an angiogenesis assay, limited data are available on the involvement of chicken macrophages in this process. Here, we describe a method to deplete macrophages in the ex ovo chick CAM assay by injection of clodronate liposomes and show that this depletion directly affects vascularisation of collagen onplants. Chicken embryos were injected intravenously with either clodronate or phosphate-buffered saline (PBS) liposomes, followed by placement of collagen type I plugs on the CAM to quantify angiogenic ingrowth. Clodronate liposome injection led to a significant 3.4-fold reduction of macrophages compared with control embryos as measured by immunohistochemistry and flow cytometry. Furthermore, analysis of vessel ingrowth into the collagen plugs revealed a significantly lower angiogenic response in macrophage-depleted embryos compared with control embryos, indicating that chicken embryonic macrophages play an essential function in the development of blood vessels. These results demonstrate that the chick CAM assay provides a promising model to investigate the role of macrophages in angiogenesis.

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Regulation and function of macrophage colony-stimulating factor (CSF1) in the chicken immune system

Cited by 25 publications

References 52 publications

Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE

Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE

Rh-CSF1 attenuates neuroinflammation via the CSF1R/PLCG2/PKCε pathway in a rat model of neonatal HIE

Depletion of Embryonic Macrophages Leads to a Reduction in Angiogenesis in the Ex Ovo Chick Chorioallantoic Membrane Assay

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