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Trends Immunol. 2019 Jun;40(6):472-481. doi: 10.1016/j.it.2019.03.009. Epub 2019 Apr 18.

Leukocyte Adhesion: Reconceptualizing Chemokine Presentation by Glycosaminoglycans.

Author information

1
Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK; These authors contributed equally. Electronic address: gerard.graham@glasgow.ac.uk.
2
University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA 92093, USA; These authors contributed equally. Electronic address: thandel@ucsd.edu.
3
Novimmune SA, 14 Chemin des Aulx, 1228 Plan les Ouates, Geneva, Switzerland; These authors contributed equally. Electronic address: amandapf@orange.fr.

Abstract

Recruitment of immune cells from the vasculature relies on the presentation of glycosaminoglycan-bound chemokines on the luminal side of vascular endothelial cells. However, the current model of chemokine-glycosaminoglycan interactions, and its implications for receptor interactions, remains poorly developed. We propose a refined 'Chemokine Cloud' model, arguing that chemokines are not presented to leukocytes bound to glycosaminoglycans, but rather, in solution while sequestered within the hydrated glycocalyx. We posit that glycosaminoglycans provide an immobilized chemokine depot maintaining a 'cloud' of 'solution-phase' chemokines within the glycocalyx, and that it is this soluble form of any given chemokine that interacts with leukocyte-bound receptors. Our proposition clarifies certain anomalies associated with the current model of chemokine-glycosaminoglycan interactions, with implications for the design of blockers of chemokine function.

KEYWORDS:

chemokines; glycocalyx; glycosaminoglycans; receptors

PMID:
31006548
DOI:
10.1016/j.it.2019.03.009
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