The Distribution of Granulocyte-Macrophage Colony-Stimulating Factor and Its Receptor in the Developing Human Fetus

Dame, John B.; Rd, Christensen; Se, Juul

doi:10.1203/00006450-199910000-00002

Cited by 48 publications

(37 citation statements)

References 27 publications

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“…GM-CSF expression in neural tissues has been well documented in several studies of fetal neurons, neuronal cell lines, and isolated microglial cells and astrocytes (13)(14)(15)(16), and we have detected GM-CSF mRNA in whole hypothalamus, forebrain, hindbrain, and cerebellum of wild-type mice (data not shown). To determine whether fasting or feeding influenced hypothalamic expression, we isolated total RNA from whole hypothalamus from fed or 48-hour-fasted rats and measured GM-CSF expression (Supplemental Figure 3B).…”

Section: Gm-csf Receptors and Gm-csf Are Expressed In Cns Cellsmentioning

confidence: 77%

“…These findings are consistent with those demonstrating immunofluorescence in neurons of the PVN and suggest that GM-CSF can act directly on neurons. GM-CSF receptor expression in neural tissues has been well documented in several studies of fetal neurons, neuronal cell lines, and isolated microglial cells and astrocytes (13)(14)(15)(16). Since GM -/-mice are completely lacking in GM-CSF expression during development, as well as adulthood, it is possible that a subset of GM-CSF-expressing CNS cell type is absent in these mice.…”

Section: Figurementioning

confidence: 99%

“…Receptors have been reported in fetal brains and isolated neurons, and from in vitro studies of isolated oligodendrocytes and astrocytes (13)(14)(15)(16). Functional GM-CSF receptors are heterodimers of single α and β subunits (17).…”

Section: Gm-csf Receptors and Gm-csf Are Expressed In Cns Cellsmentioning

confidence: 99%

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GM-CSF action in the CNS decreases food intake and body weight

Reed

Clegg

Smith

et al. 2005

Journal of Clinical Investigation

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Many proinflammatory cytokines, such as leptin, play key roles in dynamic regulation of energy expenditure and food intake. The present work tested a role for the proinflammatory cytokine GM-CSF. Central but not peripheral administration of GM-CSF to adult rats significantly decreased food intake and body weight for at least 48 hours. Similar results were observed following central administration of GM-CSF in mice. GM-CSF receptor immunoreactivity was found on neurons within the paraventricular and arcuate nuclei of the hypothalamus. GM-CSF-deficient (GM -/-) mice weighed more and had significantly higher total body fat than wildtype (GM +/+ ) mice. Energy expenditure in GM -/-mice was decreased compared with that in GM +/+ mice. Taken together, these findings demonstrate that GM-CSF signaling in the CNS can regulate energy homeostasis. IntroductionMaintenance of energy homeostasis requires the accurate matching of caloric intake to caloric expenditure over time. When such energy balance is maintained, stored energy in the form of adipose mass is defended. A wide range of CNS systems have been linked to the control of energy balance by their responses to peripheral signals that reflect the status of stored energy. These systems provide potential targets for therapeutic intervention to treat the growing problem of obesity. One peripheral signal regulating these central circuits is the adipocyte-derived cytokine leptin. Low levels of leptin signaling stimulate increased food intake and weight gain (1). A wider role for leptin as a cytokine has become apparent, as new functions that extend beyond energy balance are uncovered. Leptin receptors (LepRs) have been detected in hematopoietic cells, and leptin induces proliferation, differentiation, and functional activation of these cells (2). These actions are analogous to those of the cytokine GM-CSF, which is used clinically to stimulate hematopoiesis (3). Moreover, both GM-CSF and leptin have proinflammatory actions that guide inflammatory and immune responses (4, 5).Since leptin and GM-CSF share overlapping functions in the periphery, we hypothesized that GM-CSF may also play an important role in regulating energy balance. Here, we report the effect of central and peripheral administration of GM-CSF in rats and mice, the distribution of GM-CSF receptor in hypothalamus, and the consequences of loss of GM-CSF signaling in mice.

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Section: Gm-csf Receptors and Gm-csf Are Expressed In Cns Cellsmentioning

confidence: 77%

Section: Figurementioning

confidence: 99%

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GM-CSF action in the CNS decreases food intake and body weight

Reed

Clegg

Smith

et al. 2005

Journal of Clinical Investigation

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“…3,6 G(M)-CSF plays an important role in normal brain and neuronal function, normal central nervous system (CNS) neurodevelopment, and neuronal repair after ischemia or trauma 3-9 independent of any effect on hematopoiesis or BM function. Normal resting human astrocytes also synthesize both G-CSF and GM-CSF.…”

Section: Normal Brain Tissue Synthesizes G(m)-csfmentioning

confidence: 99%

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

Kast¹,

Hill

Wion

et al. 2017

Tumour Biol.

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Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain-be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation-increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration-and European Medicines Agency-approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.

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“…However, although GM-CSF is produced during the neonatal period, it is scarcely present in the adult CNS (20,21). In the normal adult CNS, the only source of GM-CSF is from peripherally primed, infiltrating T cells, which patrol the brain parenchyma (22,23).…”

mentioning

confidence: 99%

Granulocyte-Macrophage Colony-Stimulating Factor Induces an Expression Program in Neonatal Microglia That Primes Them for Antigen Presentation

Belyanskaya

Riese

et al. 2002

The Journal of Immunology

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Neonatal microglial cells respond to GM-CSF and M-CSF by acquiring different morphologies and phenotypes. To investigate the extent and consequences of this process, a global gene expression analysis was performed, with significant changes in transcript levels confirmed by biochemical analyses. Primary murine microglial cells underwent substantial expression reprogramming after treatment with GM-CSF or M-CSF with many differentially expressed transcripts important in innate and adaptive immunity. In particular, many gene products involved in Ag presentation were induced by GM-CSF, but not M-CSF, thus potentially priming relatively quiescent microglia cells for Ag presentation. This function of GM-CSF is distinct from its primary function in cell proliferation and survival.

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The Distribution of Granulocyte-Macrophage Colony-Stimulating Factor and Its Receptor in the Developing Human Fetus

Cited by 48 publications

References 27 publications

GM-CSF action in the CNS decreases food intake and body weight

GM-CSF action in the CNS decreases food intake and body weight

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

Granulocyte-Macrophage Colony-Stimulating Factor Induces an Expression Program in Neonatal Microglia That Primes Them for Antigen Presentation

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