Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a protein secreted by macrophages, T cells, mast cells, NK cells, endothelial cells and fibroblasts. GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Granulocyte macrophage–colony stimulating factor (GM-CSF) is secreted in response to inflammatory stimuli such as LPS, IL-1, and TNF-α by a variety of different cells, including endothelium, fibroblasts, muscle cells, and macrophages, and by activated T cells. GM-CSF is glycosylated in its mature form.
Alternate Names - CSF2, GMCSF, colony stimulating factor 2, CSF
Homology Across Species
Bos taurus (cattle) GM-CSF – 100%
Bos mutus (wild yak) GM-CSF – 99%
Bison bison bison (bison) GM-CSF – 98%
Bos indicus (zebu) GM-CSF – 98%
More - https://blast.ncbi.nlm.nih.gov/
Transcriptomic Profiles of Monocyte-Derived Macrophages in Response to Escherichia coli is Associated with the Host Genetics.
Emam M, Cánovas A, Islas-Trejo AD, Fonseca PAS, Medrano JF, Mallard B.
Sci Rep. 2020 Jan 14;10(1):271. doi: 10.1038/s41598-019-57089-0.
Applications: Generation of monocyte-derived macrophages in culture.
Reactive Nitrogen Species (RNS) are a group of bactericidal molecules produced by macrophages in response to pathogens in a process called oxidative burst. Nitric oxide (NO-) is a member of RNS produced from arginine by inducible Nitric Oxide Synthase (iNOS) enzyme. The activity of iNOS and production of NO- by macrophages following stimulation is one of the indicators of macrophage polarization towards M1/proinflammatory. Production of NO- by bovine monocyte-derived macrophage (MDM) and mouse peritoneal macrophages has been shown to be strongly associated with host genetic with the heritability of 0.776 in bovine MDM and 0.8 in mouse peritoneal macrophages. However, the mechanism of genetic regulation of macrophage response has remained less explored. In the current study, the transcriptome of bovine MDMs was compared between two extreme phenotypes that had been classified as high and low responder based on NO- production. The results showed that 179 and 392 genes were differentially expressed (DE) between high and low responder groups at 3 and 18 hours after exposure to Escherichia coli, respectively. A set of 11 Transcription Factors (TFs) (STAT1, IRF7, SPI1, STAT4, IRF1, HIF1A, FOXO3, REL, NFAT5, HIC1, and IRF4) at 3 hours and a set of 13 TFs (STAT1, IRF1, HIF1A, STAT4, ATF4, TP63, EGR1, CDKN2A, RBL1, E2F1, PRDM1, GATA3, and IRF4) at 18 hours after exposure to E. coli were identified to be differentially regulated between the high and low responder phenotypes. These TFs were found to be divided into two clusters of inflammatory- and hypoxia-related TFs. Functional analysis revealed that some key canonical pathways such as phagocytosis, chemotaxis, antigen presentation, and cell-to-cell signalling are enriched among the over-expressed genes by high responder phenotype. Based on the results of this study, it was inferred that the functional characteristics of bovine MDMs are associated with NO-based classification. Since NO- production is strongly associated with host genetics, this study for the first time shows the distinct proinflammatory profiles of macrophages are controlled by the natural genetic polymorphism in an outbred population. In addition, the results suggest that genetics can be considered as a new dimension in the current model of macrophage polarization which is currently described by the combination of stimulants, only.
Short communication: Effect of granulocyte-macrophage colony-stimulating factor on neonatal calf peripheral blood neutrophil function in vitro.
Roach HB, Brester JL, Abuelo A.
J Dairy Sci. 2020 Jan;103(1):864-870. doi: 10.3168/jds.2019-17441. Epub 2019 Nov 14.
Applications: Stimulation of neutrophils in culture.
The effect of host genetics on in vitro performance of bovine monocyte-derived macrophages.
Emam M, Tabatabaei S, Sargolzaei M, Sharif S, Schenkel F, Mallard B.
J Dairy Sci. 2019 Oct;102(10):9107-9116. doi: 10.3168/jds.2018-15960. Epub 2019 Aug 7.
Applications: In vitro transformation of monocytes to macrophages
The dynamic interaction between the host and pathogens, along with environmental factors, influences the regulation of mammalian immune responses. Therefore, comprehensive in vivo immune-phenotyping during an active response to a pathogen can be complex and prone to confounding effects. Evaluating critical fundamental aspects of the immune system at a cellular level is an alternative approach to reduce this complexity. Therefore, the objective of the current study was to examine an in vitro model for functional phenotyping of bovine monocyte-derived macrophages (MDM), cells which play a crucial role at all phases of inflammation, as well influence downstream immune responses. As indicators of MDM function, phagocytosis and nitric oxide (NO-) production were tested in MDM of 16 cows in response to 2 common bacterial pathogens of dairy cows, Escherichia coli and Staphylococcus aureus. Notable functional variations were observed among the individuals (coefficient of variation: 33% for phagocytosis and 70% in the production of NO-). The rank correlation analysis revealed a significant, positive, and strong correlation (rho = 0.92) between NO- production in response to E. coli and S. aureus, and a positive but moderate correlation (rho = 0.58) between phagocytosis of E. coli and S. aureus. To gain further insight into this trait, another 58 cows were evaluated solely for NO- response against E. coli. The pedigree of the tested animals was added to the statistical model and the heritability was estimated to be 0.776. Overall, the finding of this study showed a strong effect of host genetics on the in vitro activities of MDM and the possibility of ranking Holstein cows based on the in vitro functional variation of MDM.
Differential Responses of Bovine Monocyte-Derived Macrophages to Infection by Neospora caninum Isolates of High and Low Virulence.
García-Sánchez M, Jiménez-Pelayo L, Horcajo P, Regidor-Cerrillo J, Ólafsson EB, Bhandage AK, Barragan A, Werling D, Ortega-Mora LM, Collantes-Fernández E.
Front Immunol. 2019 Apr 30;10:915. doi: 10.3389/fimmu.2019.00915. eCollection 2019.
Applications: Cell Culture Stimulation of Bovine PBMCs with GM-CSF
Abstract
Neospora caninum, a protozoan parasite closely related to Toxoplasma gondii, represents one of the main causes of abortion in cattle. Macrophages (MØs) are mediators of the innate immune response against infection and likely one of the first cells encountered by the parasite during the host infection process. In this study, we investigated in vitro how high or low virulent isolates of N. caninum (Nc-Spain7 and Nc-Spain1H, respectively) interact with bovine monocyte-derived MØs and the influence of the isolate virulence on the subsequent cellular response. Both isolates actively invaded, survived and replicated in the MØs. However, Nc-Spain7 showed a higher invasion rate and a replication significantly faster, following an exponential growth model, whereas Nc-Spain1H presented a delayed replication and a lower growth rate without an exponential pattern. N. caninum infection induced a hypermigratory phenotype in bovine MØs that was characterized by enhanced motility and transmigration in vitro and was accompanied by morphological changes and abrogated extracellular matrix degradation. A significantly higher hypermotility was observed with the highly virulent isolate Nc-Spain7. Nc-Spain1H-infected MØs showed elevated reactive oxygen species (ROS) production and IL12p40 expression, which also resulted in increased IFN-γ release by lymphocytes, compared to cells infected with Nc-Spain7. Furthermore, IL-10 was upregulated in MØs infected with both isolates. Infected MØs exhibited lower expression of MHC Class II, CD86, and CD1b molecules than uninfected MØs, with non-significant differences between isolates. This work characterizes for the first time N. caninum replication in bovine monocyte-derived MØs and details isolate-dependent differences in host cell responses to the parasite.
Coordinated Role of Toll-Like Receptor-3 and Retinoic Acid-Inducible Gene-I in the Innate Response of Bovine Endometrial Cells to Virus.
Carneiro LC, Bedford C, Jacca S, Rosamilia A, de Lima VF, Donofrio G, Sheldon IM, Cronin JG.
Front Immunol. 2017 Aug 23;8:996. doi: 10.3389/fimmu.2017.00996. eCollection 2017.
Applications: Stimulation of bovine dendritic cells using bovine IL-4 and bovine GM-CSF to produce monocyte-derived dendritic cells in culture.
Monocyte-derived dendritic cells from late gestation cows have an impaired ability to mature in response to E. coli stimulation in a receptor and cytokine-mediated fashion.
Pomeroy B, Sipka A, Klaessig S, Schukken Y.
Vet Immunol Immunopathol. 2015 Sep 15;167(1-2):22-9. doi: 10.1016/j.vetimm.2015.06.016. Epub 2015 Jul 2.
Applications: IL-10 and IL-12 were used as ELISA standards. IL-4 and GM-CSF were used to stimulate monocytes in culture. MHC II, CD14, and CD80 antibodies were used to look at cell surface receptors by flow cytometry.
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