About CCL5 / RANTES:
Chemokine (C-C motif) ligand 5, also known as CCL5, is a protein that within the human body is encoded with the CCL5 gene. This gene is also known as RANTIES which means regulated on activation, normal T cell expression and secretion.
CCL5 is a 8kDa protein that is classified as a chemotactic cytokine or a chemokine. Chemokines are a small family of cytokines (cytokines create signals using proteins that are secreted by the cells). The names of these cells are linked to their ability to induce direct chemotaxis in cell groups that are located nearby and are responsive - these are known as chemotactic cytokines.
These proteins are classified as chemokines because of how they behave and because of the structure that they have. These proteins also mediate chemotaxis and are around 8 to 10 kilodaltons in mass. They also normally have four cysteine residues that are kept within conserved locations - it’s these residues that allow them to form their three dimensional shape.
Many chemokines are pro-inflammatory and can be induced during an immune response to recruit cells of the immune system to the site of an infection. However, other chemokines are considered homeostatic and focus on controlling the migration of cells during normal processes of tissue development and maintenance. They are found in the vertebrates, some viruses and bacteria, but none have been found for other invertebrates.
Chemokines are classified in four main subfamilies, these are CXC, CC, CX3C, and XC. Each of these proteins take their proteins from biological effects by interacting with g-protein linked transmembrane receptors known as chemokine receptors - these are found on the surface of target cells.
CCL5 is chemotactic for T cells, eosinophils, and basophils, and is able to play an active role in recruiting leukocytes into inflammatory sites where they are needed. With assistance from specialist cytokines that are released from the T cells, CCL5 can induce proliferation and activation of specific natural-killer cells from CHAK ( CC-Chemokine-activated killer) cells.
CCL5 is also an HIV suppressive factor that is released from CD8+T cells. This chemokine has been localized to chromosome 17 within humans.
RANTIES was first found in a search for genes that were expressed ‘late’ (3-5 days) after the T cell activation. It was determined that CC chemokine was what it was and that it was expressed in more than 100 human diseases.
RANTIES expression is regulated by the T lymphocytes by Kruppel like factor 13. RANTIES with the related chemokines, has been found to be a natural HIV-suppressive factor that is secreted by activated CD8+T cells, in addition to other immune cells. More recently, RANTIES protein has been genetically engineered for in vivo production by Lactobacillus bacteria, with a solution being developed that could be a possible HIV entry-inhibiting topical microbicide.
CCL5 has been determined to interact well with CCR3, CCR5 and CCR1. CCL5 has also been found to activate the G-protein coupled receptor GPR75.
Up until recently, chemokines were seen mainly as ‘gatekeepers’ of immunity and inflammation within the body. However, new research has suggested that cancer cells subvert the usual chemokine system and that these proteins and their receptors become an important part of the tumour microenvironment.