Human GM-CSF (Granulocyte/Monocyte-Colony Stimulating Factor) is a differentially glycosylated factor produced mainly by activated T cells and macrophages. Endothelial cells and fibroblasts can also produce GM-CSF after exposure to TNF-α, IL-1, IL-2 and IFN-γ. GM-CSF is found associated with extracellular matrix and in membrane-bound formats too. GM-CSF stimulates proliferation, activation and differentiation of macrophages and granulocytes and their progenitors.
<0.001 EU per 1 μg of the peptide by the LAL method
Investigated for use/treatment in adverse effects (chemotherapy) and bone marrow transplant.
Examples of Clinical Use:
Adverse effects (chemotherapy) and bone marrow transplant
Mechanism of action:
This drug activates mononuclear phagocytes, promotes migration of epithelial cells, and further regulates cytokine production. In 2 recent placebo-controlled studies involving venous leg ulceration, subcutaneous perilesional injections of recombinant human granulocyte-macrophage colony-stimulating factor were found to be significantly better than placebo in the time to complete wound healing. In other studies, recombinant human granulocyte-macrophage colony-stimulating factor was administered topically to wounds. Several case reports have also demonstrated the use of recombinant human granulocyte-macrophage colony-stimulating factor for postsurgical wounds, chronic leg ulcers of sickle cell anemia patients, and refract and refractory pyoderma gangrenosum.
Granulocyte-macrophage colony-stimulating factor, commonly known as GM-CSF, is a cytokine that plays a vital role in the regulation of the immune system. It was first discovered in the 1970s and was initially named Colony-Stimulating Factor. Later, it was identified as a granulocyte-macrophage colony-stimulating factor due to its ability to stimulate the production and differentiation of granulocytes and macrophages.
The gene encoding GM-CSF is located on chromosome 5 in humans. It consists of six exons and five introns. The protein structure of GM-CSF consists of 127 amino acids and has a molecular weight of approximately 14.6 kilodaltons. It forms a compact, globular structure that is stabilized by four disulfide bonds.
GM-CSF protein function
The primary function of GM-CSF is to stimulate the production, differentiation, and activation of various immune cells, particularly granulocytes and macrophages. It acts as a growth factor for these cells, promoting their development from hematopoietic stem cells in the bone marrow. Additionally, GM-CSF enhances the functional activities of these cells, such as phagocytosis and antigen presentation.
GM-CSF protein-related signaling pathways
GM-CSF exerts its effects on target cells through specific signaling pathways. One of the key pathways involved is the JAK-STAT pathway. Upon binding of GM-CSF to its receptor on the cell surface, it triggers the activation of Janus kinases (JAKs), which subsequently phosphorylate and activate signal transducer and activator of transcription (STAT) proteins. Activated STAT proteins translocate to the nucleus and regulate the transcription of target genes involved in immune cell proliferation and differentiation.
Another important signaling pathway activated by GM-CSF is the PI3K/Akt pathway. This pathway plays a crucial role in cell survival and proliferation. GM-CSF stimulates the activation of phosphatidylinositol 3-kinase (PI3K), which leads to the activation of Akt (protein kinase B). Akt regulates multiple downstream targets involved in cell survival, protein synthesis, and glucose metabolism.
GM-CSF protein-related diseases and the role of GM-CSF in diseases
GM-CSF is implicated in various diseases, both in physiological and pathological contexts. In physiological conditions, GM-CSF plays a role in the regulation and maintenance of the immune system. It helps in the clearance of infections and promotes tissue repair by enhancing the recruitment and activation of immune cells.
On the other hand, dysregulation of GM-CSF expression or signaling can lead to pathological conditions. Overexpression of GM-CSF is associated with several autoimmune and inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, and inflammatory lung diseases. In these diseases, GM-CSF contributes to the recruitment and activation of inflammatory cells, leading to tissue damage and chronic inflammation.
The application of GM-CSF protein in medicine
Due to its role in immune regulation and tissue repair, GM-CSF has been studied and utilized in various therapeutic approaches. One application of GM-CSF is in cancer immunotherapy. It has been used as an adjuvant in cancer vaccines to enhance the immune response against tumor antigens.
Additionally, GM-CSF can be administered as a recombinant protein to boost the production and function of immune cells in patients with compromised immune systems, such as those undergoing chemotherapy or bone marrow transplantation. It can promote the recovery of neutrophils and macrophages, thus reducing the risk of infections.
List of drug candidates related to GM-CSF protein
There are several drug candidates that target the GM-CSF pathway. One example is Mavrilimumab, a monoclonal antibody that binds to the GM-CSF receptor alpha subunit and inhibits the signaling of GM-CSF. It is being investigated for the treatment of rheumatoid arthritis.
Lenzilumab is another monoclonal antibody that targets GM-CSF. It binds to GM-CSF and prevents its interaction with its receptor, thereby inhibiting downstream signaling. Lenzilumab is undergoing clinical trials for the treatment of COVID-19, as it has the potential to modulate the excessive immune response seen in severe cases of the disease.
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