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Review
. 2012 May 15;246(1-2):1-9.
doi: 10.1016/j.jneuroim.2012.02.016. Epub 2012 Mar 22.

Chemokine receptor CXCR2: physiology regulator and neuroinflammation controller?

Mike Veenstra  1 , Richard M Ransohoff
Affiliations
Review

Chemokine receptor CXCR2: physiology regulator and neuroinflammation controller?

Mike Veenstra et al. J Neuroimmunol. .

Abstract

The innate immune system is a crucial component of inflammatory reactions, while the central nervous system (CNS) is the most vulnerable site of the body to inflammatory tissue injury. Neuroinflammatory brain pathologies are disorders in which the CNS is threatened by its own immune system. Chemokine receptor CXCR2 and its ligands have been implicated in several neuroinflammatory brain pathologies, as well as in neutrophil recruitment and in the developmental positioning of neural cells. This review focuses on the basics of CXCR2, its regulating role in bone marrow neutrophil recruitment, oligodendrocyte progenitor cell positioning and neural repair mechanisms, as well as its diverse roles in neuroinflammatory brain pathologies.

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Figures

Figure 1
Figure 1. CXCR2 structure and ligand binding concept
The CXCR2 chemokine receptor is compromised of seven transmembrane segments, three extracellular and three intracellular loops, an extracellular N-terminal domain, and an intracellular C-terminal domain. It contains a DRY motif on the second intracellular loop, functioning as G-protein docking site, and other protein docking sites as the LLKIL motif on the C-terminus. The CXCR2 ligand N-terminus binds with the N-terminal domain of the receptor (site 1), after which the ELR+ motif of the chemokine binds with the second and third extracellular loop of the receptor (site 2), to control the binding and to activate receptors signaling pathways.
Figure 2
Figure 2. Hypothetical model of CXCR2’s regulating role in two separate recruiting events
Upon acute injury, two different reactions take place simultaneously: release of neutrophils from the bone marrow (i) and local neutrophil recruitment (ii).

  1. Injury activates γδ and natural killer T cells, which produces IL-17A. This induces transcription of G-CSF in the bone marrow, which activates TPO. Stimulation by TPO inhibits CXCL12-CXCR4 binding and activates the release of CXCR2 ligands from megakaryocytes. The release of the CXCR2 ligands and weakening of the CXCR2 binding, leads to mobilization of neutrophils from the bone marrow.

  2. Activation of inflammasomes leads to IL-1β release and stimulation of local CXCR2 ligand production, inducing a subsequential production of TNF-α and LTB4, therewith activating integrins and selectins on the endothelial cells close the site of the lesion. CXCR2 ligands are presented at the site of the lesion, creating a chemotactic gradient for the recruitment of neutrophils through the interaction of CXCR2 and CXCR2 ligands.

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References

    1. Ahuja SK, Murphy PM. The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor. J. Biol Chem. 1996;271:20545–20550. - PubMed
    1. Ahuja SK, Ozcelik T, Milatovitch A, Francke U, Murphy PM. Molecular evolution of the human interleukin-8 receptor gene cluster. Nat. Genet. 1992;2:31–36. - PubMed
    1. Allen SJ, Crown SE, Handel TM. Chemokine: receptor structure, interactions, and antagonism. Annu. Rev. Immunol. 2007;25:787–820. - PubMed
    1. Amiri KI, Ha HC, Smulson ME, Richmond A. Differential regulation of CXC ligand 1 transcription in melanoma cell lines by poly(ADP-ribose) polymerase-1. Oncogene. 2006;25:7714–7722. - PMC - PubMed
    1. Anisowicz A, Bardwell L, Sager R. Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells. Proc. Natl. Acad. Sci. U. S. A. 1987;84:7188–7192. - PMC - PubMed

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