Stromal Cell-Derived Factor-1 alpha (SDF-1α), also known as C-X-C motif chemokine 12 (CXCL12), is a chemokine protein encoded by the CXCL12 gene in humans . This protein plays a crucial role in various physiological and pathological processes, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis .
SDF-1α is produced in two main forms, SDF-1α (CXCL12a) and SDF-1β (CXCL12b), through alternative splicing of the same gene . The protein belongs to the intercrine alpha (chemokine CXC) family, characterized by the presence of four conserved cysteines that form two disulfide bonds . The recombinant form of SDF-1α, produced in E. coli, is a non-glycosylated polypeptide chain containing 68 amino acids and has a molecular mass of approximately 8 kDa . The His Tag is a sequence of histidine residues added to the N-terminus of the protein to facilitate purification and detection .
SDF-1α functions as a potent chemoattractant for T-lymphocytes and monocytes but not neutrophils . It activates the C-X-C chemokine receptor CXCR4, inducing a rapid and transient rise in intracellular calcium ions and chemotaxis . Additionally, SDF-1α binds to the atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1 .
SDF-1α is ubiquitously expressed in many tissues and cell types, including the brain, thymus, heart, lung, liver, kidney, spleen, platelets, and bone marrow . During embryogenesis, it directs the migration of hematopoietic cells from the fetal liver to the bone marrow and the formation of large blood vessels . SDF-1α also functions as a pre-B cell growth factor in the presence of interleukin-7 (IL-7) and is a ligand for CXCR4 or the orphan receptor LESTR/fusin .
Mutations in the CXCL12 gene are associated with resistance to human immunodeficiency virus type 1 (HIV-1) infections . Additionally, CXCL12 signaling has been observed in several cancers, and the gene contains one of 27 single nucleotide polymorphisms (SNPs) associated with an increased risk of coronary artery disease .