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What Are Chemokines?

By Emma Lloyd
Updated: May 17, 2024

Chemokines are a class of proteins which are integral to a process called cell trafficking, in which migratory cells are given chemical "instructions" on where in the body they should move to. Various different types of chemokines have specific roles in regulating the movement of different types of cells, including cells involved in tissue development or maintenance and cells of the immune system. This process is an essential part of the body's repair system and of the immune system, because it ensures that cells migrate to the right areas of the body when they are required.

The family of chemokine proteins was first discovered in the late 1980s, when a protein previously known as interleukin-8 was reclassified as CXC chemokine ligand 8, or CXCL8. This reclassification occurred due to the discovery that the protein was able to activate a type of immune cell called a neutrophil. Chemokines are sometimes called pro-inflammatory activation-inducible cytokines. Previously, these proteins have had several other names, including interkines, and the SIG, SCY, and SIS family of cytokines.

Subsequent research found that chemokines act using a mechanism called chemotaxis, allowing the proteins to act as molecular signals to attract various types of cells to sites where they are needed. The term chemotaxis describes the way cells follow a chemical gradient created when cells release chemokines into the tissues. For example, cells at the site of injury or infection release these proteins into surrounding tissues. At the site itself, chemokine concentration is very high, but the concentration decreases relative to the distance from the site. Immune cells are thus able to locate the site of injury or infection by following the chemical gradient from low to high chemokine concentration.

Chemokine proteins are generally small, and tend to have a high level of sequence homology. This refers to the fact that, at the level of amino acid sequence within the protein, there is a great deal of similarity. The main differences in amino acid sequence between different chemokine types relate to the types of cells they are chemotactic for. For example, some have an amino acid sequence called an ELR sequence motif. Those that do have the sequence are mainly involved in chemotaxis for neutrophils, while those that don't have the sequence regulate the movement of several other immune cell types, excluding neutrophils.

The primary role of chemokine proteins in immune system chemotaxis suggests that they might be important therapeutic intervention targets for certain diseases. One such candidate is known as CCL5, or RANTES. This protein is involved in regulating the inflammatory immune response, and might therefore be a suitable therapeutic target in certain types of autoimmune disease and cancer, as well as disorders of the central nervous system, and even heart disease. The central role of CCL5 in inflammation also means the protein might serve as a diagnostic marker, and as an indicator of prognosis for these diseases.

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