| Description: |
The only CX3C chemokine identified to date is CX3C chemokine ligand 1 (CX3CL1), also known as fractalkine or neurotactin. With its unique CX3CR1 receptor [], it is involved in adherence to the endothelium of the inflammatory monocyte population [].CX3CL1 and CXCL16 represent two exceptions among the members of the chemokine family. In addition to their chemokine domain, they possess three other domains: a mucin-like stalk, a transmembrane (TM) domain, and a cytosolic tail [, ]. When interacting with their cognate receptors (CX3CR1 and CXCR6, respectively), these chemokines induce cell-cell adhesion []. CX3CL1 and CXCL16 can also be cleaved by metalloproteinases to yield a soluble form that is chemotactic [, ]. CX3CL1 also binds and activates integrins through its chemokine domain in a CX3CR1-dependent and independent manner, binding to the classical ligand-binding site (RGD-binding site, site 1) or to a second site (site 2) in integrins, respectively [].Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions,and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role []. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [], and endothelial cells, where they may act as either angiogenic or angiostatic factors [].The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors []. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [, ]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1). |
