Function and Types of Chemokines
- Chemokines form a concentration gradient to attract cells towards higher concentrations.
- They act as chemoattractants to guide the migration of cells.
- Some chemokines control immune system cells during immune surveillance.
- Chemokines have roles in development, promoting angiogenesis, and guiding cell maturation.
- Inflammatory chemokines recruit immune cells to sites of infection or tissue damage.
- Homeostatic chemokines are constitutively produced and responsible for basal leukocyte migration.
- Inflammatory chemokines are formed under pathological conditions and participate in the inflammatory response.
Homing and Types of Cells Attracted by Chemokines
- Chemokines manage the migration of leukocytes in inflammatory and homeostatic processes.
- Homeostatic chemokines are produced in thymus and lymphoid tissues for basal leukocyte migration.
- Inflammatory chemokines are produced in high concentrations during infection or injury.
- Homeostatic chemokines include CCL19 and CCL21, which route antigen-presenting cells to lymph nodes.
- Inflammatory chemokines include CCL2, CCL3, and CXCL1, attracting inflammatory leukocytes to damaged areas.
- Chemokines attract monocytes/macrophages, T-lymphocytes, mast cells, eosinophils, and neutrophils to specific sites.
Structural Characteristics of Chemokines
- All chemokines have a Greek key structure stabilized by disulfide bonds.
- Chemokines are small proteins with a molecular mass of 8-10 kDa.
- They share gene sequence and amino acid sequence homology, with approximately 20-50% identity to each other.
- Chemokines possess conserved amino acids important for their 3-dimensional structure, including four cysteines that form a characteristic Greek key shape.
- Chemokines are produced as pro-peptides and undergo cleavage during secretion.
- The N-terminal end of the mature protein contains the first two cysteines, followed by a loop, helices, and strands connected by turns.
CC and CXC Chemokines
- CC chemokines have two adjacent cysteines near their amino terminus.
- There are at least 27 distinct members of this subgroup reported for mammals.
- CC chemokines induce the migration of monocytes, NK cells, and dendritic cells.
- Examples of CC chemokines include MCP-1 (CCL2) and CCL5 (RANTES).
- CXC chemokines have two N-terminal cysteines separated by one amino acid.
- There are 17 different CXC chemokines described in mammals.
- ELR-positive CXC chemokines induce the migration of neutrophils.
- Examples of CXC chemokines include IL-8 (CXCL8) and CXCL13.
Chemokines and Their Roles in Inflammation, Neuromodulation, and Metastasis
- Chemokines are responsible for recruiting immune cells to sites of inflammation.
- Chemokine receptors on immune cells facilitate their migration towards the site of inflammation.
- Chemokines regulate the adhesion and extravasation of immune cells during inflammation.
- Chemokines also influence the activation and polarization of immune cells at the site of inflammation.
- Chemokines play a role in neuromodulation and are expressed in the central nervous system.
- Chemokines can influence synaptic transmission and neuronal plasticity.
- Homeostatic chemokine receptors are involved in maintaining immune cell distribution in different tissues.
- Dysregulation of homeostatic chemokine receptors can lead to abnormal immune cell accumulation in certain organs.
- Chemokine receptors also play a role in the metastasis of cancer cells to specific organs.
- Inhibition of chemokines and chemokine receptors has shown promise in the treatment of inflammatory and autoimmune diseases.
Chemokines (from Ancient Greek χῠμείᾱ (khumeíā) 'alchemy', and κῑ́νησῐς (kī́nēsis) 'movement'), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.
| Small cytokines (intecrine/chemokine), interleukin-8 like | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 Solution structure of interleukin-8, a chemokine of the CXC subfamily | |||||||||||
| Identifiers | |||||||||||
| Symbol | IL8 | ||||||||||
| Pfam | PF00048 | ||||||||||
| InterPro | IPR001811 | ||||||||||
| PROSITE | PDOC00434 | ||||||||||
| SCOP2 | 3il8 / SCOPe / SUPFAM | ||||||||||
| |||||||||||
This article needs additional citations for verification. (April 2013) |
Cytokine proteins are classified as chemokines according to behavior and structural characteristics. In addition to being known for mediating chemotaxis, chemokines are all approximately 8–10 kilodaltons in mass and have four cysteine residues in conserved locations that are key to forming their 3-dimensional shape.
These proteins have historically been known under several other names including the SIS family of cytokines, SIG family of cytokines, SCY family of cytokines, Platelet factor-4 superfamily or intercrines. Some chemokines are considered pro-inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection, while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Chemokines are found in all vertebrates, some viruses and some bacteria, but none have been found in other invertebrates.
Chemokines have been classified into four main subfamilies: CXC, CC, CX3C and C. All of these proteins exert their biological effects by interacting with G protein-linked transmembrane receptors called chemokine receptors, that are selectively found on the surfaces of their target cells.
