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Review
. 2016 Jun;99(6):851-5.
doi: 10.1189/jlb.1MR1015-457R. Epub 2015 Dec 29.

Chemokine interaction with synergy-inducing molecules: fine tuning modulation of cell trafficking

Valentina Cecchinato  1 , Gianluca D'Agostino  1 , Lorenzo Raeli  1 , Mariagrazia Uguccioni  2
Affiliations
Review

Chemokine interaction with synergy-inducing molecules: fine tuning modulation of cell trafficking

Valentina Cecchinato et al. J Leukoc Biol. 2016 Jun.

Abstract

Directed migration and arrest of leukocytes during homeostasis, inflammation, and tumor development is mediated by the chemokine system, which governs leukocyte migration and activities. Although we understand well the effects of different chemokines one by one, much less was known about the potential consequences of the concomitant expression of multiple chemokines or of their interaction with inflammatory molecules on leukocyte migration and functions. In the past 10 yr, several studies revealed the existence of additional features of chemokines: they can antagonize chemokine receptors or synergize with other chemokines, also by forming heterocomplexes. Moreover, recent data show that not only chemokines but also the alarmin high-mobility group box 1 can for a complex with CXCL12, enhancing its potency on CXCR4. The molecular mechanism underlying the effect of the heterocomplex has been partially elucidated, whereas its structure is a matter of current investigations. The present review discusses the current knowledge and relevance of the functions of heterocomplexes formed between chemokines or between the chemokine CXCL12 and the alarmin high-mobility group box 1. These studies highlight the importance of taking into account, when approaching innovative therapies targeting the chemokine system, also the fact that some chemokines and molecules released in inflammation, can considerably affect the activity of chemokine receptor agonists.

Keywords: CXCL12; HMGB1; cell migration; chemokine activities.

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Figures

Figure 1.
Figure 1.. Synergism induced by the formation of heterocomplexes.
(A) Heterocomplex formed between 2 chemokines renders the agonist more potent on the selective receptor. (B) HMGB1 forms a heterocomplex with CXCL12 enhancing CXCL12 potency on CXCR4.
See this image and copyright information in PMC

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