Chemokines and Chemokine Receptors

Manel Juan, Servei d'Immunologia, Barcelona, Catalonia, Spain
Roger Colobran, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IICSGTiP), Badalona, Catalonia, Spain

Published online: December 2009

DOI: 10.1002/9780470015902.a0000933.pub2

Chemokines (CKs) are a family of small proteins secreted by a great variety of cell types. Their name (derived from chemoattractant cytokines) is due to their ability to induce directed chemotaxis in nearby responsive cells. Some CKs are considered pro-inflammatory and can be induced during an immune response to promote cells of the immune system to a site of infection, whereas others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. CKs are found in all vertebrates, some viruses and some bacteria. These proteins exert their biological effects by interacting with G protein-linked transmembrane receptors called chemokine receptors (CKRs) that are selectively found on the surfaces of their target cells. CKs play roles in cell maturation and differentiation, infection, autoimmunity, cancer and, in general, in any situation where immune components are involved. Their role in human immunodeficiency virus (HIV) infection is of special relevance.

Key concepts:

  • Chemokines (CKs), as chemoattractant cytokines, are pivotal elements for defining immune cell localization and, therefore, efficient immune responses.
  • Beyond their role in chemotaxis, CKs and their receptors develop several physiopathological functions: angiogenesis, haematopoiesis, growth regulation, embryologic development, evolution of tumours, etc.
  • CKs have three types of receptors: ‘classical’ G protein-coupled receptors (GPCRs), decoy receptors and glycosaminoglycans (GAGs).
  • After activation, GPCRs become either partially or totally desensitized to repeated stimulation with the same or other agonists; desensitization is critical for maintaining the capacity of the cell to sense a chemoattractant gradient.
  • Decoy receptors are ‘silent’ receptors that control the CK activity through regulation of CK levels in the body.
  • CK immobilization through the GAG interaction stabilizes the formation of CK gradients and enhances their concentration at the site of production.
  • All CKs have a common structure, being the first couple of cysteines (Cs) a distinctive element that allows classifying them in CC, CXC, CX3C and C CK families.
  • Most of inflammatory CK genes are clustered in two main chromosomal regions: the CXC cluster, located in chromosome 4q12–21, and the CC cluster, located in chromosome 17q11.2.
  • The ‘evolutionary choice’ of HIV-1 to exploit CKRs as cellular entry gateways has turned their CK ligands into endogenous antiviral factors that can variably modulate viral transmission, disease progression and vaccine responses.

Keywords: leucocyte; chemoattractant; recirculation; inflammation; HIV

Figure 1. Chemokine – chemokine receptor structure and interaction. (a) Proposed general topography of the CCL4 CK. Amino acids forming the three sheets and the helix are depicted in orange and green, respectively. The two disulfide bridges that stabilize the tertiary structure are shown as red lines connecting the four Cs. (b) Proposed membrane topography of the human CCR5 receptor. Membrane-spanning helices are defined on the basis of hydropathy analysis. CHO represents potential N-linked glycosylation sites. Residues shown in blue represent the DRYLAVHA sequence motif characteristic of CKRs. Residues in red represent Ser and Thr residues that are potential phosphorylation sites for specific receptor kinases during desensitization. Note that the CCL4 N-terminus interact with the extracellular part of CCR5 receptor.
Figure 2. Proposed multistep mechanism of entry of HIV-1 by interaction with CD4 and chemokine receptors.
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 Further Reading
    book Fulton A (ed.) (2009) Chemokine Receptors in Cancer. Totowa, NJ: Humana Press.
    book Mahalingam S (2004) Chemokines in Viral Infections. Austin, TX: Landes Bioscience.
    book Oppenheim J and Feldman M (2001) Cytokine Reference: Volume 1 and Volume 2. San Diego, CA: Academic Press.
    book Schwiebert L, Benos D and Simon S (2005) Chemokines, Chemokine Receptors and Disease. San Diego, CA: Academic Press.
    book Vaddi K, Keller M and Newton RC (1997) The Chemokine Factsbook. San Diego, CA: Academic Press.

Related Sub-Topics:

Cytokines | Proteins: Structure, Function, Metabolism
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Article Title: Chemokines and Chemokine Receptors
 
How to Cite close
Juan, Manel, and Colobran, Roger(Dec 2009) Chemokines and Chemokine Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000933.pub2]