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).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.CXCR1 and CXCR2, also known as interleukin 8 receptor alpha and beta, respectively [], are closely-related receptors. They act as specific receptors for the CXCL8 and CXCL6 chemokines, which have a glutamate-leucine-arginine (ELR) motif in their N-terminal domains []. CXCR2 also binds additional ELR motif-containing CXC chemokines (such as CXCL1, CXCL2, CXCL3, CXCL5 and CXCL7) with high affinity [].CXCR1 and CXCR2 are expressed on all granulocytes, monocytes, and mast cells and on some CD8+ T-cells and CD56+ natural killer (NK) cells []. Equal amounts of CXCR1 and CXCR2 are present on neutrophils [, , , , ], but it appears that monocytes and positive lymphocytes express more CXCR2 than CXCR1 [].This entry represents both CXCR1 and CXCR2.
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).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.CXCR1 and CXCR2, also known as interleukin 8 receptor alpha and beta, respectively [], are closely-related receptors. They act as specific receptors for the CXCL8 and CXCL6 chemokines, which have a glutamate-leucine-arginine (ELR) motif in their N-terminal domains []. CXCR2 also binds additional ELR motif-containing CXC chemokines (such as CXCL1, CXCL2, CXCL3, CXCL5 and CXCL7) with high affinity [].CXCR1 and CXCR2 are expressed on all granulocytes, monocytes, and mast cells and on some CD8+ T-cells and CD56+ natural killer (NK) cells []. Equal amounts of CXCR1 and CXCR2 are present on neutrophils [, , , , ], but it appears that monocytes and positive lymphocytes express more CXCR2 than CXCR1 [].This entry represents CXCR1
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).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.CXCR1 and CXCR2, also known as interleukin 8 receptor alpha and beta, respectively [], are closely-relatedreceptors. They act as specific receptors for the CXCL8 and CXCL6 chemokines, which have a glutamate-leucine-arginine (ELR) motif in their N-terminal domains []. CXCR2 also binds additional ELR motif-containing CXC chemokines (such as CXCL1, CXCL2, CXCL3, CXCL5 and CXCL7) with high affinity [].CXCR1 and CXCR2 are expressed on all granulocytes, monocytes, and mast cells and on some CD8+ T-cells and CD56+ natural killer (NK) cells []. Equal amounts of CXCR1 and CXCR2 are present on neutrophils [, , , , ], but it appears that monocytes and positive lymphocytes express more CXCR2 than CXCR1 [].This entry represents CXCR2. The angiogenic effects of CXCL8 in intestinal microvascular endothelial cells are mediated by this receptor []. It has been suggested that the receptor may be a potential theraputic target in acute lung injury [].
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).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.This entry represents the N-terminal region of the CXC type 4 chemokine receptor. CXCR4 and its ligand stromal cell-derived factor-1 (also known as CXCL12) are essential for proper fetal development. CXCR4 is also the major coreceptor for T-tropicstrains of Human immunodeficiency virus 1, and SDF-1 inhibits HIV-1 infection. Additionally, SDF-1 and CXCR4 mediate cancer cell migration and metastasis. The N-terminal domain of most chemokine receptors is the ligand binding domain and so the N-terminal domain of CXCR4 is the binding site for SDF-1 [].
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).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.This entry represents CXCR3, which is expressed in natural killer cells and activated T lymphocytes but not in resting T lymphocytes, B lymphocytes, monocytes or granulocytes [, ]. CXCR3 also appears to be constitutively expressed on endothelial cells of medium and large blood vessels []. CXCR3 is able to regulate leukocyte trafficking and binding to various chemokines inducing various cellular responses, most notably integrin activation, cytoskeletal changes and chemotactic migration [, , , ]. The main role of CXCR3 is the selective recruitment of effector T cells in both normal tissues and inflammation []and it is involved in a number of T cell-mediated inflammatory diseases, such as autoimmune diseases, delayed-type hypersensitivity responses, certain viral diseases and acute transplant rejection []. It has been implicated in atherosclerosis [], pulmonary fibrosis [], type 1 diabetes []and nephrotoxic nephritis [], and has been implicated in wound healing [].CXCR3 is the receptor for CXCL9 (Mig), CXCL10 (IP10) and CXCL11 (I-TAC), [, , , ], which are upregulated in response to interferon-gamma and are potent chemoattractants for activated T cells [, ]. All three chemokines elicit an increase in intracellular Ca2+ levels and activate phosphoinositide 3-kinase and mitogen-activated protein kinase (MAPK) []. CXCR3 is also capable of binding a number of CC chemokines with moderate affinity, including CCL11 (eotaxin), CCL13, CCL20, CCL7, CCL5 []. However, it has been reported that CCL11, despite binding with high affinity, may be neither an agonist or an antagonist of the CXCR3 receptor, but sequesters available CCL11 resulting in a lowered response at other receptors [].
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).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.This entry represents CXC chemokine receptor 6 (CXCR6) also known as cluster of differentiation 186 and is a receptor for chemokine CXCL16. CXCL16 does not activate any other known chemokine receptor, this interaction is highly specific and unique []. Binding of CXCL16 to CXCR6 causes chemotactic migration in activated T cells [, ]however, CXCR6 is a weak mediator of chemotaxis []. The resultant chemotactic response is sensitive to pertussis toxin and results in calcium mobilisation [, ]. CXCR6 is expressed in lymphoid tissues and activated T cells and is induced in peripheral blood leukocytes []and found on natural killer cells []. A number of roles have been suggested for CXCR6 and subset-specific immune responses may be regulated by cell-cell contacts between activated subsets of T cells expressing CXCR6 and antigen presenting cells expressing CXCL16. CXCR6 may also be involved in cell-cell contacts during chronic inflammation []. Additional roles for the receptor include T cell migration in the splenic red pulp, thymocyte development and effector T cell trafficking []. It has been shown that CXCR6 acts as a coreceptor for T cell line-tropic and macrophage-tropic HIV-1 strains, and may play a role in the establishment and progression of HIV infection [, ].
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).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.This entry represents CXC chemokine receptor type 5 (CXCR5), also known as cluster of differentiation 185 or Burkitt lymphoma receptor 1, which acts as a receptor for CXCL13. Upon binding to CXCR5, it causes mobilisation of intracellular calcium and chemotaxis []. CXCR5 is specifically expressed in B cells and lymphatic tissues, as well as in spleen [, ]and is expressed by human CD34(-) mesenchymal progenitor cells and immortalized mesenchymal stem cell lines [].B lymphocytes expressing CXCR5 migrate in a concentration dependent manner in response to CXCL13, which does not induce chemotaxis in T lymphocytes, monocytes or neutrophils. This selectivity for B lymphocytes is unique among the chemokines. CXCR5 also plays an essential role in B cell migration [], lymphocyte homing []and in the development of normal lymphoid tissue [, ]. It has also been shown that CD4+CXCR5+ T cells expressing CXCR5 play a protective role in the immune response against mycobacterium tuberculosis (Mtb) infection, highlighting a potential use for TB vaccine design and therapy [].
