CSF-1 stimulates glucose uptake in murine bone marrow-derived macrophages

doi:10.1016/0006-291X(86)90301-3

Biochemical and Biophysical Research Communications

Volume 138, Issue 1, 16 July 1986, Pages 445-454

https://doi.org/10.1016/0006-291X(86)90301-3 Get rights and content

Abstract

³H-2-deoxyglucose was used as an isotopic tracer for the measurement of glucose uptake into quiescent murine bone marrow derived macrophages. A purified colony stimulating factor (CSF-1) was shown to stimulate ³H-2-deoxyglucose uptake in a dose-dependent manner. This stimulation was rapid, with a maximal effect seen at 20–30 minutes after growth factor addition. Both the inhibition by cytochalasin B and also the relative degree of competition by high concentrations of a series of glucose analogues suggest that the basal and CSF-1 stimulated 2-deoxyglucose uptake occur via a carrier facilitated D-glucose transport system.

The data indicate that a purified growth factor can increase the glucose uptake in macrophages, a finding which could be relevant to the survival and/or the proliferative response of this and other haemopoietic cell types.

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Citation Excerpt :
Early work indicated that M1 macrophages have a voracious appetite for glucose that is fluxed toward glycolytic pathway to generate ATP supporting phagocytic and microbicidal functions (Fasting et al., 1979; Mills et al., 2016; Russell et al., 2019). Limitation of glucose uptake by 2‑deoxyglucose (2DG) inhibited macrophage activation in vitro and dampened inflammation in in vivo models (Hamilton et al., 1986; Michl et al., 1976). 2DG also blunts LPS-induced interleukin-1β but not TNF-α in mouse macrophages (Tannahill et al., 2013).
Brown and subcutaneous adipose tissues play a key role in non-shivering thermogenesis both in mice and human, and their activation by adrenergic stimuli promotes energy expenditure, reduces adiposity, and protects against age-related metabolic diseases such as type 2 diabetes (T2D). Low-grade inflammation and insulin resistance characterize T2D. Even though the decline of thermogenic adipose tissues is well-established during ageing, the mechanisms by which this event affects immune system and contributes to the development of T2D is still poorly defined. It is emerging that activation of thermogenic adipose tissues promotes type 2 immunity skewing, limiting type 1 inflammation. Of note, metabolic substrates sustaining type 1 inflammation (e.g. glucose and succinate) are also used by activated adipocytes to promote thermogenesis. Keeping in mind this aspect, a nutrient competition between adipocytes and adipose tissue immune cell infiltrates could be envisaged. Herein, we reviewed the metabolic rewiring of adipocytes during thermogenesis in order to give important insight into the anti-inflammatory role of thermogenic adipose tissues and delineate how their decline during ageing may favor the setting of low-grade inflammatory states that predispose to type 2 diabetes in elderly. A brief description about the contribution of adipokines secreted by thermogenic adipocytes in modulation of immune cell activation is also provided. Finally, we have outlined experimental flow chart procedures and provided technical advices to investigate the physiological processes leading to thermogenic adipose tissue impairment that are behind the immunometabolic decline during aging.
Ceramide 1-phosphate stimulates glucose uptake in macrophages
2013, Cellular Signalling
Citation Excerpt :
Our previous work demonstrated that C1P is a major regulator of macrophage growth and death (for a review, see [8]), and more recently we found that it is a potent stimulator of macrophage migration [10]. These vital biological functions require high energy levels to be accomplished, and it is known that the major source of metabolic energy in macrophages is glucose [54–56]. The data reported in this work demonstrate that C1P stimulates glucose uptake as well as ATP production in RAW264.7 macrophages.
It is well established that ceramide 1-phosphate (C1P) is mitogenic and antiapoptotic, and that it is implicated in the regulation of macrophage migration. These activities require high energy levels to be available in cells. Macrophages obtain most of their energy from glucose. In this work, we demonstrate that C1P enhances glucose uptake in RAW264.7 macrophages. The major glucose transporter involved in this action was found to be GLUT 3, as determined by measuring its translocation from the cytosol to the plasma membrane. C1P-stimulated glucose uptake was blocked by selective inhibitors of phosphatidylinositol 3-kinase (PI3K) or Akt, also known as protein kinase B (PKB), and by specific siRNAs to silence the genes encoding for these kinases. C1P-stimulated glucose uptake was also inhibited by pertussis toxin (PTX) and by the siRNA that inhibited GLUT 3 expression. C1P increased the affinity of the glucose transporter for its substrate, and enhanced glucose metabolism to produce ATP. The latter action was also inhibited by PI3K- and Akt-selective inhibitors, PTX, or by specific siRNAs to inhibit GLUT 3 expression.
Phosphatidylinostitol-3 kinase and phospholipase C enhance CSF-1-dependent macrophage survival by controlling glucose uptake
2009, Cellular Signalling
Colony stimulating factor-1 (CSF-1)-dependent macrophages play crucial roles in the development and progression of several pathological conditions including atherosclerosis and breast cancer metastasis. Macrophages in both of these pathologies take up increased amounts of glucose. Since we had previously shown that CSF-1 stimulates glucose uptake by macrophages, we have now investigated whether glucose metabolism is required for the survival of CSF-1-dependent macrophages as well as examined the mechanism by which CSF-1 stimulates glucose uptake. Importantly, we found that CSF-1-induced macrophage survival required metabolism of the glucose taken up in response to CSF-1 stimulation. Kinetic studies showed that CSF-1 stimulated an increase in the number of glucose transporters at the plasma membrane, including Glut1. The uptake of glucose induced by CSF-1 required intact PI3K and PLC signalling pathways, as well as the downstream effectors Akt and PKC, together with a dynamic actin cytoskeleton. Expression of constitutively active Akt partially restored glucose uptake and macrophage survival in the absence of CSF-1, suggesting that Akt is necessary but not sufficient for optimal glucose uptake and macrophage survival. Taken together, these results suggest that CSF-1 regulates macrophage survival, in part, by stimulating glucose uptake via Glut1, and PI3K and PLC signalling pathways.
Correlations between <sup>18</sup>F-FDG uptake by bone marrow and hematological parameters: measurements by PET/CT
2006, Nuclear Medicine and Biology
The aim of this study was to investigate the correlations between ¹⁸F-FDG uptake by bone marrow and various hematological parameters.
Forty-eight patients who underwent FDG-PET/CT studies and also received hematological examinations within 5 days before or after the PET study were included in this study. All patients had not received chemotherapy. FDG uptake by bone marrow was measured as a standardized uptake value (SUV) on three-dimensional PET/CT fusion images, and the uptake ratio (UR) of the SUV of bone marrow to the SUV of longitudinal dorsal muscle was calculated. The correlations between the SUV and the UR of bone marrow and various hematological parameters were evaluated.
Bone marrow FDG uptake was strongly correlated with the white blood cell counts but was not significantly correlated with the red blood cell and platelet counts. The neutrophil count was significantly correlated with bone marrow FDG uptake but the lymphocyte count was not.
FDG uptake by bone marrow was specifically correlated with the neutrophil count, suggesting that the FDG uptake by bone marrow reflects marrow metabolism that is mainly regulated by granulocyte progenitors and stimulated by endogenous hematopoietic growth factors. They may also be helpful in interpreting PET images, especially for diagnosing bone marrow involvement by malignancy.
Correlation of hematologic parameters with bone marrow and spleen uptake in FDG PET
2005, Revista Espanola de Medicina Nuclear
Valorar la correlación existente entre los parámetros hematológicos y la captación de FDG en médula ósea (MO) y bazo en la PET.
29 pacientes (pts) con linfoma de Hodgkin remitidos para un estudio inicial con FDG PET antes de comenzar el tratamiento y sin evidencia de afectación en MO, fueron incluidos en el estudio. En 18 pts sin afectación esplénica también se valoro la captación de FDG en el bazo. La captación en MO y bazo se clasificó de acuerdo a una escala visual de tres puntos, y se determinó si era homogénea o difusa. También se realizó un análisis semi-cuantitativo por medio de unos índices de captación obtenidos a través de unas regiones de interés, en médula ósea y bazo, en relación con otras en pulmón derecho e hígado. Se calcularon unos coeficientes de correlación entre la escala visual y los indices semi-cuantitativos en médula ósea y bazo, con las cifras de hemoglobina (Hb), leucocitos y plaquetas en sangre.
En 27/29 pts la captación de FDG en MO y en 18/18 pts la captación en bazo fue homogénea. Se objetivó una correlación directa entre las cifras de leucocitos y la captación de FDG en MO y bazo. La correlación era menor y además inversa con las cifras de Hb (esto es, cuanto más baja la Hb mas alta la captación en MO). Las correlaciones mas bajas se obtuvieron con la cifras de plaquetas.
Los diferentes parámetros hematológicos pueden llegar a afectar la captación de FDG en MO y bazo. El conocimiento de esta correlación puede ayudar a la mejor interpretación de los estudios FDG PET.
To assess the relationship between various hematologic parameters and bone marrow (BM) and splenic uptake of FDG in PET imaging.
29 patients with Hodgkin's disease (HD) referred for baseline FDG PET imaging before treatment and without evidence of bone marrow (BM) involvement were included in the study. Splenic uptake also was analyzed in 18 patients without splenic involvement. BM and splenic activity were visually graded on a 3 point scale. Activity pattern was classified as homogeneous or heterogeneous. Semi-quantitative analysis was also performed by drawing regions of interest (ROI) over the spine and spleen. ROIs also were drawn over right lung and liver. FDG uptake ratios for the spine and spleen in comparison with the lung and liver were generated. Visual scoring of marrow and splenic uptake, and the various ratios were correlated with hemoglobin (Hb), white blood cell (WBC), and platelet counts, and correlation coefficients were calculated.
In 27/29 patients (93 %) BM and in 18/18 patients (100 %) spleen uptake was diffuse. There was a direct correlation between BM and spleen uptake of FDG with increasing WBC, which was stronger than the inverse correlation seen with Hb (the lower the Hb the greater the uptake). Correlation with platelet counts was weaker.
There is a correlation between hematologic parameters such as Hb, WBC and platelet counts and the uptake of FDG in BM and spleen in PET imaging. Knowledge of this correlation should help to better interpret and understand PET imaging.
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Les cytokines sont des médiateurs protéiques sécrétés par les leucocytes. Elles jouent un rôle primordial dans la coordination de la réponse de l'organisme à l'infection. Outre leur rôle de médiateurs immunitaires, il semblerait que les cytokines soient également impliquées dans certaines modifications métaboliques lors des infections bactériennes. Notre but ici est de faire le point sur le rôle éventuel des cytokines dans le contrôle du métabolisme glucidique. Lors des infections, la production hépatique de glucose est augmentée, ainsi que l'utilisation de ce substrat énergétique par divers tissus. Il a été démontré que certaines cytokines, telles que le tumor necrosis factor (TNF) et l'interleukine-1, peuvent stimuler le transport et le catabolisme du glucose par divers types cellulaires. De plus, les cytokines induisent des modifications de la sécrétion d'hormones glucorégulatrices semblables à celles observées chez l'animal et chez l'homme lors des infections. Bien que ne constituant pas une preuve absolue, ces observations suggèrent que les cytokines jouent un rôle important dans l'homéostasie glucidique dans ce contexte. Puisque ces médiateurs constituent un maillon essentiel de la réponse immunitaire, une meilleure connaissance de l'interaction entre la sécrétion des cytokines et le contrôle du métabolisme glucidique apporterait d'autres éléments à notre compréhension de la réponse de l'organisme aux infections.
Cytokines are protein mediators secreted by leukocytes. They are responsible in large measure for orchestrating the host response against infection. In addition to their role as immune modulators, several observations have been made that implicate the cytokines as mediators of the metabolic alterations during bacterial sepsis. The purpose of this paper is to review existing information on the potential role cytokines have in regulating carbohydrate metabolism. Sepsis generally results in an increased production of glucose by the liver and an enhanced utilization of this fuel by many tissues in the body. Cytokines like tumor necrosis factor and interleukin-1 have been demonstrated to directly stimulate glucose uptake and catabolism in several cell types. In addition, cytokines alter the secretion of glucoregulatory hormones in a manner that is similar to the changes seen in animals or humans compromised with infection. While not definitive, these findings indicate that the cytokines produced during an infection likely play an important role in regulating glucose homeostasis during infection. Because cytokines are important to host defense against delivery, understanding the interaction between cytokine production and the regulation of glucose metabolism will advance our knowledge of the host response to infections.

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CSF-1 stimulates glucose uptake in murine bone marrow-derived macrophages

Abstract

J. Immunol. Methods

J. Biol. Chem

Biochem. Biophys. Res. Comm

Cell

Differentiation

Biochem. Biophys. Res. Comm

J. Biol. Chem

J. Immunol. Methods

Int. Rev. Cytol

Nature

The hemopoietic colony stimulating factors