Chemokines

doi:10.1016/j.dci.2003.09.006

Developmental & Comparative Immunology

Volume 28, Issue 5, 3 May 2004, Pages 443-460

https://doi.org/10.1016/j.dci.2003.09.006 Get rights and content

Abstract

Chemokines are small proteins that control cellular migration. An extensive family of these molecules has been described in mammals containing nearly 50 members. Within this family are four groups, each defined by the different spacing of two N-terminal cysteines, which form disulphide bonds with two other cysteine residues to create the tertiary structure characteristic of chemokines. Recent evidence shows the chemokine family is not unique to mammals, with several members also identified in birds, amphibians and fish, including a primitive vertebrate, the lamprey. Although there is less evidence to define the roles of chemokines in these lower vertebrates, structural similarities allow some predictions to their function, against which further studies are being made. Additionally, some microorganisms (particularly viruses) appear to have copied genes for chemokines, presumably to confuse the immune system of their host. This review aims to bring together the current information concerning identified chemokines throughout vertebrates and microorganisms.

Introduction

A large multifunctional family of cytokines, known as chemokines (CHEMOtactic cytoKINES), that induce the migration of cells to sites of infection or injury has been described. Functionally chemokines fall into two main categories. Some are homeostatic and are produced and secreted constitutively. These are generally involved in lymphocyte trafficking, immune surveillance and localisation of lymphocytes with antigen in the lymphatic system [1]. Other chemokines are only produced by cells during infection or following a pro-inflammatory stimulus and prompt the migration of leukocytes to an injured or infected site. Such inflammatory chemokines can also activate cells to raise an immune response and commence the wound healing process.

Chemokines are structurally related, with most containing four invariant cysteine residues. Depending on the arrangement of the first two of these cysteines, chemokines are divided into four subfamilies; CXC (α), CC (β), C (γ) and CX₃C (δ) [2]. Chemokines are produced as pro-peptides and are cleaved during secretion to produce an active mature protein [3] that functions by activating G-protein-coupled receptors.

Section snippets

Mammalian chemokines

The majority of information concerning chemokines has been derived from studies in mammals. Mammalian chemokines are listed in Table 1 in their respective subfamilies. Throughout this review, mammalian chemokines will be referred to by recently defined nomenclature [2]. Common synonyms for these mammalian chemokines can also be found in Table 1. Most mammalian chemokines belong to the CXC and CC subfamilies that contain 16 and 28 members, respectively.

CXC chemokines

Birds appear to possess members of at least three of the subfamilies described for mammalian chemokines. The first identified was a CXC chemokine from the chicken Gallus gallus that is known as cCAF (for chicken chemotactic and angiogenic factor). cCAF, the product of a gene called 9E3/CEF4, is structurally similar to mammalian CXCL8 with relatively high amino acid identity (51%) to human CXCL8 [49]. Interestingly, the functional (N-terminal) end of mature cCAF is more homologous structurally

Amphibian chemokines

Few chemokine sequences exist for amphibians at this time. The only published example is of a recently described CXCL12-like molecule identified in the African clawed frog Xenopus laevis [58] called xSDF-1. xSDF-1 was identified by screening a Xenopus spleen cDNA library as a transcript encoding 94 amino acids. It shares 64–66% amino acid identity with mammalian CXCL12 and 26% identity to CXCL1. The mature peptide of xSDF-1 is predicted to contain 73 amino acids giving a molecular mass of

Fish chemokines

Much interest has been generated in the study of fish chemokines in recent years. As a result, several sequences have now been described for chemokines and their receptors in various fish species.

Viral chemokines

Viruses are known to adopt molecular piracy and mimicry in order to overcome the immune system of their host organism. This phenomenon, it is believed, has led to the identification of several chemokine sequences within virus genomes and is particularly common in the herpesvirus family. The genome of Kaposi's sarcoma-associated herpesvirus-8 (HHV-8), contains three CC chemokine-like sequences known as viral macrophage inflammatory protein-I, -II and -III (vMIP-I, vMIP-II and vMIP-III) whose

Summary

Multiple chemokine types have been described, not just in mammals, but also in fish and birds suggesting that similar control mechanisms of cellular migration exist throughout vertebrates. From the presence of both CXC and CC chemokines in all these vertebrates, it can be predicted that these two subfamilies arose before fish split from the main vertebrate lineage. Although there are scant chemokine sequences available at this time for amphibians and reptiles, it is possible that these animals

Acknowledgements

This work was supported by a grant from the Wellcome Trust (059180).

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Chemokines

Abstract

Introduction

Section snippets

Mammalian chemokines

CXC chemokines

Amphibian chemokines

Fish chemokines

Viral chemokines

Summary

Acknowledgements

Immunol Lett

Blood

J Biol Chem

J Biol Chem

J Biol Chem

Cell Immunol

Biochem Biophys Res Commun

Frontiers Neuroend

J Biol Chem

J Biol Chem

J Biol Chem

Vet Immunol Immunopath

Blood

Cytokine

Am J Pathol

Blood

J Biol Chem

Blood

FEBS Lett

Cytokine

Genomics

Biochem Biophys Res Commun

Int J Biochem Cell Biol

Cytokine

Cytokine

Cytokine

Gene

Gene

Dev Comp Immunol

Cytokine

Fish Shellfish Immunol

Mol Immunol

Mech Dev

Cytokine

Fish Shellfish Immunol

Fish Shellfish Immunol

Vaccine

Blood

Semin Immunol

Virology

FEMS Immunol Med Microbiol

Trends Immunol

Structure, function, and inhibition of chemokines

Ann Rev Pharmacol Toxicol

International union of pharmacology. XXII. Nomenclature for chemokine receptors

Pharmacol Rev

Chemotactic factors, neuropeptides, and other ligands for seven transmembrane receptors

The functional role of the ELR motif in CXC chemokine-mediated angiogenesis

J Biol Chem

The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes

Science