Greater than 96.0% as determined by:
(a)Analysis by RP-HPLC.
(b)Analysis by SDS-PAGE.
MAPTRSPNPV TRPWKHVDAI KEALSLLNDM RALENEKNED VDIISNEFSI
QRPTCVQTRL KLYKQGLRGN LTKLNGALTM IASHYQTNCP PTPETDCEIE
VTTFEDFIKN LKGFLFDIPF DCWKPVQK.
GM-CSF was first identified in the conditioned media of mouse lung tissue following lipopolysaccharide (LPS) injection, which triggered the proliferation of bone marrow-derived macrophages and granulocytes . It acts on mature myeloid cells as a pro-survival, activation, and differentiation factor . GM-CSF promotes the survival and activation of macrophages, neutrophils, and eosinophils, as well as the maturation of dendritic cells (DCs) .
The GM-CSF receptor is composed of one α chain and one β chain, with low and high-affinity binding to GM-CSF, respectively . The β chain is shared with the receptors for IL-3 and IL-5 . Upon binding of GM-CSF to its receptor, Janus-kinase-2 (JAK-2) is recruited to the cytoplasmic domain of the β chain, leading to the activation of JAK-2 and subsequent phosphorylation of STAT-5 . This signaling pathway induces the migration of STAT-5 dimers to the nucleus, promoting the transcription of various genes involved in cell differentiation .
GM-CSF has significant pro-inflammatory functions and contributes to the pathogenicity of Th17 cells in the development of Th17-mediated autoimmune diseases . It stimulates the activation and migration of myeloid cells to inflammation sites, promoting the survival of target cells and the renewal of effector granulocytes and macrophages . An imbalance in GM-CSF production or signaling can lead to harmful inflammatory conditions . GM-CSF has been implicated in autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA), where it plays a pathogenic role . Conversely, it has a protective role in other autoimmune diseases where humoral responses are detrimental, such as myasthenia gravis (MG), Hashimoto’s thyroiditis (HT), inflammatory bowel disease (IBD), and systemic lupus erythematosus (SLE) .
Given its role in inflammation and autoimmune diseases, GM-CSF has become a target for therapeutic intervention. Inhibition of GM-CSF has shown significant beneficial effects in animal models of autoimmune diseases . Clinical trials targeting GM-CSF in rheumatoid arthritis patients have demonstrated rapid and significant efficacy with no serious side effects .