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Chemokines

Chemokines are usually small sized cytokines or signalling proteins which are responsible for inducing chemotaxis within nearby cells and their actions are mediated through the binding to G protein-coupled receptor (GPCR), resulting in the stimulation of receptor specific intracellular signalling pathways.

Chemokines are a family of signalling proteins or small cytokines that are predominately secreted from cells and their molecular weight can range between 8-10 kDa. They all share a similar structure which usually consists of four cysteine residues, conserved locations are key to forming their three dimensional shape. The name chemokine is derived from their ability in inducing directed chemotaxis within nearby responsive cells (they are essentially chemotactic cytokines). Chemotaxis refers to when cells are directing their movement according to the presence of chemicals within their surrounding environment. The action of a chemokine is mediated through its interaction with a member of the G protein-coupled receptor (GPCR) family. These transmembrane receptors are always coupled to an intracellular G-protein and this is responsible for stimulating a signalling pathway inside the cell upon its activation.

FUNCTIONS OF CHEMOKINES

The major functions of chemokines is managing the migration of leukocytes (often known as homing) in the respective anatomical locations in homeostatic and inflammatory processes.

  1. Homeostatic: These are constitutively produced in certain tissues (thymus and lymphoid) and are mainly responsible for the basal leukocyte migration. These include the following chemokines CCL14, CCL19, CCL20, CCL21, CCL25, CCL27, CXCL12 and CXCL13.
  2. Inflammatory: These are essentially produced at elevated levels during an infection or injury and they are responsible for determining the migration of inflammatory leukocytes into the damaged area. Some of the typical inflammatory chemokines include CCL2, CCL3, CCL5, CXCL1, CXCL2 and CXCL8.

TYPES OF CHEMOKINES

Chemokines can be classified into four main subfamilies: CXC, CC, CX3C and XC. All of these proteins are known to exert their biological effects by interacting with specific G protein-linked transmembrane receptors that are called chemokine receptors and these are selectively found on the surfaces of their target cells. Up to date around nineteen different types of chemokine receptors have been identified in mammals. They are also found predominantly on the surface of leukocytes or white blood cells.

  • CXC: There are approx. 17 different CXC chemokines which have been identified in mammals and they have been sub-divided into two categories; those containing a specific amino acid sequence (or motif) ofglutamic acid-leucine-arginine (ELR for short) immediately before the first cysteine of the CXC motif (known as ELR-positive) and those without an ELR motif (known as ELR-negative).
  • CC: This represents the largest group and currently there are over 27 distinct members that have been reported for mammals (CCL-1 to CCL-28). These are also called beta-chemokine proteins and can contain either four or six cysteines. These CC chemokines function to induce the migration of monocytes, dendritic and NK cells. Two of the most popular ones are monocyte chemoattractant protein-1 (MCP-1 or CCL2) and RANTES (CCL5).
  • CX3C: This group contains three amino acids between the two There has only been one discovered to date which has been called fractalkine (CX3CL1), it can serve either as an adhesion molecule or a chemoattractant since it is attached to the surface of the cell that expresses it and it can also be secreted.
  • XC: The final group can also be called gamma chemokines and are different from the other groups above because they only contain two cysteines, one cysteine at the N-terminal and the other cysteine downstream. There are only two that have be identified for this group and they are called lymphotactin-alpha (XCL1) and lymphotactin-beta (XCL2).

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