Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a monomeric glycoprotein that acts as a cytokine in humans. Macrophages, mast cells, T cells, endothelial cells, fibroblasts, and natural killer cells, secrete GM-CSF. Although the release of human GM-CSF is local, it can act in a paracrine fashion to recruit circulating monocytes, lymphocytes, and neutrophils to enhance host defense mechanisms. Unlike colony-stimulating factor 3 that specializing in the proliferation and maturation of neutrophils, GM-CSF stimulates a spectrum of cell types, especially eosinophils and macrophages.
The extent to which a drug is glycosylated plays a crucial role in drug/body interactions. The human GM-CSF gene is present on chromosome region 5q31. Researchers first cloned GM-CSF in 1985, which soon gave way to three potential drugs with a varying degree of glycosylation:
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Human GM-CSF protein functions as a growth factor for WBC. In lieu, GM-CSF growth factor will stimulate stem cells to produce monocytes and granulocytes. Monocytes then exit the circulation and enter tissues, where they mature into dendritic cells and macrophages. They activate a small set of macrophages that can rapidly increase in numbers, which plays a crucial role in fighting infections. Thus, GM-CSF immunotherapy is a key member of the immune/inflammatory cascade.
Through STAT-protein, GM-CSF helps develop the immune system and defense mechanisms against infections. GM-CSF along with STAT proteins activates macrophages to impede fungal survival. They deprive the cells of free zinc and increase the reactive oxygen species production that helps culminate cell toxicity. The function of GM-CSF is to enhance neutrophil migration and acts as an embryokine to aid in embryonic development.
How long do you think it takes for a new drug to get approved in the US? About 12-15 years, that’s roughly 1/3rd duration of the entire professional career for any of us. Next, how much investment do you think is required to bring a new drug to market?
We, at NorthEast BioLabs, use GM-CSF ELISA, MSD, and Luminex assay to detect granulocyte-macrophage colony-stimulating factor in your sample. We can detect GM-CSF protein in serum, plasma, and cell/tissue culture supernatant. Following is a brief Luminex protocol.
The assay to test the GM-CSF structure and its function begins with 80 μl of wash buffer in each well. We shake it for 10 mins and decant the wells. Once the residue is removed, we add standard, control or samples in the appropriate wells followed by assay buffer and beads to all wells and incubate the wells overnight at 4℃. After the bead captures an analyte from the sample, we introduce a biotinylated detection antibody in each well and incubate them for 1 hr at RT. Post incubation, 20 μl of streptavidin-phycoerythrin, a reporter molecule, and incubated for 30 mins at RT. We then wash the wells with a wash buffer, add 70 μl of drive or sheath fluid and read the plate on a suitable Luminex platform.
The GM CSF Luminex assay help to quantify fluorescent reporter signals. The assay is highly sensitive, with an inter-assay precision of < 20.8% and intra-assay precision of < 2.7%. The assay is also accurate, with an accuracy of 94% recovery in serum matrix.
GM-CSF protein is a crucial immune modulator and hematopoietic growth factor. Studies have found high levels of GM-CSF in joints of rheumatoid arthritis patients, and blocking them seems to reduce the damage in patients. Drugs such as otilimab works on a similar mechanism of blocking and weakening the GM-CSF structure.
Early studies on Granulocyte-macrophage colony-stimulating factor as an immunosuppression therapy for critical illness shows promising results in restoring neutrophil and monocyte functions. Because of its macrophage activity and ability to mature dendritic cells, current research is centered on using granulocyte-macrophage colony-stimulating factor as an immune adjuvant. Research has shown that GM-CSF effectively treats neutropenia in AIDS and cancer patients. Research is also exploring another protein, anti-GM CSF that blocks the binding of GM-CSF to its receptor as an anti- GM-CSF test.
Explore more about GM-CSF and GM-CSF assays with the resources below.
https://www.nature.com/articles/7310017
https://www.sciencedirect.com/topics/medicine-and-dentistry/granulocyte-macrophage-colony-stimulating-factor
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/granulocyte-macrophage-colony-stimulating-factor
https://pubmed.ncbi.nlm.nih.gov/16474424/
http://chemocare.com/chemotherapy/drug-info/gm-csf.aspx
Brain-Derived Neurotrophic Factor
Granulate Colony Stimulation Factor
Epidermal growth factor
Fas Ligand
Granulocyte Macrophage Colony Stimulating Factor
Leukemia Inhibitory Factor
Luteinizing hormone
Macrophage Migration Inhibitory Factor
Interferon Beta
Interferon Gamma
Transforming Growth Factor Beta 1
B Type Natriuretic Peptide
Glial Fibrillary Acidic Protein
Cystatin C
Hepatocyte Growth Factor
Interferon Alpha 2
Tumor Necrosis Factor Alpha
