Anatomy & Organs

Chemokines – structure, function & diseases

Chemokine

Chemokines are small signaling proteins that trigger chemotaxis (migration) of cells . Most of these cells are immune cells. Thus, the chemokines are responsible for the effective functioning of the immune system .

What are chemokines?

Chemokines are small proteins belonging to the cytokine family . They cause cells to migrate. These are mainly immune cells that should quickly reach the appropriate site of an injury or infection.

The chemokines are produced by the cells, which are also supposed to attract them. On the surface of these cells are receptors that allow the chemokines to dock. The signaling molecules are divided into inflammatory and homeostatic chemokines. In most cases, these are inflammatory chemokines. They attract immune cells to their destination, which immediately trigger inflammatory processes to fight off infections. Inflammatory chemokines are always produced at the site of injury or infection by the immune cells present there in order to attract further immune cells.

Homeostatic chemokines are constantly being produced, even when there is no infection. They serve to monitor healthy tissue. Chemokines have a chemotaxic effect on such immune cells as monocytes , macrophages , keratinocytes , fibroblasts , platelets , endothelial cells, T cells, stoma cells, neutrophilic granulocytes , and dendritic cells. They are also formed by these cells as signaling substances in order to attract similar cells when needed.

Anatomy & Structure

Chemokines are small protein chains of 75 to 125 amino acids each . At the terminal end of the chain are one or two cysteine ​​residues. Cysteine ​​is a sulfur-containing amino acid that can form disulfide bridges in the molecule. The cysteine ​​residues now form sulfide bridges within the protein chain.While the amino acid sequence varies within the chemokine family of proteins, the tertiary structure remains the same for all chemokines. The main body is formed as a three-strand antiparallel sheet with beta structure. At the carboxy terminus, the chain ends with an alpha helix. This is where the cysteine ​​residues are located. There are four structures in which these terminal cysteine ​​residues can be arranged. Each structure symbolizes a family of chemokines. Thus, two cysteine ​​residues can follow one after the other. The corresponding chemokine family is called the CC family. If another amino acid is inserted between the cysteine ​​residues, it is in the CXC family. The CX3C family contains two cysteine ​​residues separated by three amino acids.

Finally, there is another family with a cysteine ​​residue, called the C family. All cysteine ​​residues form a sulfide bridge within the chain. Each chemokine family has different functions. The exact structure of the chemokines is still not fully understood. The chemokines do not necessarily need tissue fluid or blood to perform their function . They can also transmit their signals via fixed structures through concentration gradients. They bind with the positive charge of their many basic amino acids to a negatively charged sugar molecule (glycosaminoglucan) on the surface of cells. It is not yet clear why they lose their function when they can no longer bind to glycosaminoglucan.

Function & Tasks

The main function of chemokines is to attract certain immune cells to places in the body that are currently more resistant to infectious invaders. This makes the immune response more effective. In most cases, they also ensure that significant inflammatory reactions develop in order to fight off the infection. They are generated at the site of injury or infection by the immune cells already present there.

The now attracted cells move in the direction of the highest concentration of chemokines. The corresponding chemokine receptors are located on their surface. The chemokines bind to these receptors , triggering a migration of the cells in the direction of the highest chemokine concentration. However, each chemokine family binds to its own receptors. The CC family ensures the migration of monocytes, lymphocytes and basophilic and eosinophilic granulocytes. The CXC family is responsible for angiogenesis (growth of blood vessels ). The CX3C family plays a role in inflammatory processes in the nervous system . Finally, the C-chemokines activate the CD8 T cells and NK cells (natural killer cells).

Diseases

When the interaction between chemokines and chemokine receptors is disturbed, the immune system malfunctions. Due to a mutation of the corresponding receptor, it is often no longer suitable for the docking of chemokines. This means that immune cells can no longer be attracted in critical situations.This malfunction then manifests itself as an immune deficiency. The so-called WHIM syndrome, a special immune deficiency, can be traced back to a chemokine receptor defect. This disease manifests itself in recurrent viral and bacterial infections. The patients show a particular susceptibility to the human papilloma virus, the infection of which manifests itself in the formation of warts. Although the bone marrow is full of T-progenitor cells, these do not migrate to the sites of infection. Selective immune deficiencies against certain pathogens are also possible. So there is a mutationa receptor for a CC family chemokine specific susceptibilities to West Nile virus. In the event of a mutation, however, the same receptor also provides hereditary immunity to the HI virus.

Certain mutations in the area of ​​the chemokine receptors can also be partly responsible for autoimmune diseases or allergies . The overproduction of certain chemokines can also lead to diseases. It was found that the development of psoriasis ( psoriasis ) is related to an overproduction of the CXC chemokine IL-8. Rheumatoid arthritis also occurs in conjunction with an overproduction of IL-8. Arteriosclerotic changes are often the result of excessive inflammatory processes, which are sometimes caused by increased chemokine activity.

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.