About SDF (CXCL12):
Chemotactic cytokines, otherwise known as chemokines, are proteins with a low molecular weight. They promote migration and adhesion of their target cell populations. They consist of four different groups, categorized by the position of their conserved NH2-terminal cysteine residues. CXC chemokines like CXCL12 have one other amino acid in between conserved NH2-terminal cysteine residues. Chemokines activate seven-transmembrane domain G protein-coupled receptors to carry out their biological functions.
Chemokines are either inflammatory or homeostatic in terms of function. CXCL12 is an example of a homeostatic CXC chemokine. It was first found as pre-B cell growth factor (PBGF), which was then found to be expressed by bone marrow stromal cells. This is why it is also called stromal cell-derived factor-1 (SDF-1).
Stromal Cell-Derived Factor Functions
CXCL12 is a CXC chemokine, which has a variety of roles in both physiological and pathological processes. Also called Stromal Cell-Derived Factor, this chemokine activates or induces migration of hematopoietic progenitor and stem cells, endothelial cells and most leukocytes. It is a factor in processes such as angiogenesis, embryogenesis and inflammation. CXCL12 exists in six splice variants in humans and interacts with the receptors CXCR4 and ACKR3, as well as by binding to glycosaminoglycans in tissues and on the endothelium.
The gene that encodes CXCL12 is located on chromosome 10q11, unlike most other CXC chemokines. CXCL12 is one of the few cytokines that show 90% or higher homology between humans and mice on both the genome and protein level.
Regulating CXCL12 activity is a most to maintain balanced homeostasis. CXCR4 only has CXCL12 as a ligand, unlike other inflammatory chemokine receptors. A lack of CXCR4 shows defective cardiac ventricular septa and embryonic hematopoiesis and neurogenesis in mice, a phenotype which is similar to CXCL12 mice. Cardiac development is also affected by ACKR3, which demonstrates that the CXCL12/CXCR4/ACKR3 system is important in cardiogenesis.
Leukocyte-derived seven-transmembrane domain receptor (LESTR) was shown to be a co-factor for human immunodeficiency virus (HIV)-1 cell entry. CXCL12 has been shown to act as the natural ligand for this receptor. It could block infection of T cells by HIV-1 strains that use LESTR/fusin as coreceptor. Because of this connection with CXCL12, LESTR/fusin was renamed CXCR4 and is now known as a chemokine receptor. CXCL12 and CXCR4 are very closely connected and the receptor is found in many cell types, including most leukocyte subsets and stem cells found in circulation and cells of lymphoid organs.
CXCL12 is continuously produced by different cell types due to its important role in homeostasis. Increased expression of CXCL12 can be induced by conditions such as hypoxia and growth arrest. The six splice variants found in humans are encoded by the same Cxcl12 gene and share the first three exons. All CXCL12 isoforms share the first 67 amino acids and have different lengths. All CXCL12 variants show anti-HIV-1 activity, however some more so than others. All the splice variants contribute to different processes in various ways. Some are also more abundant than others in adult tissues.