Leukocyte adhesion: reconceptualizing chemokine presentation by glycosaminoglycans

Graham, G. J. , Handel, T. M. and Proudfoot, A. E.I. (2019) Leukocyte adhesion: reconceptualizing chemokine presentation by glycosaminoglycans. Trends in Immunology, 40(6), pp. 472-481. (doi: 10.1016/j.it.2019.03.009) (PMID:31006548)

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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.

Item Type:Articles
Additional Information:G.J.G. is supported by a Medical Research Council Programme Grant and a Wellcome Trust Investigator Award, he is also recipient of funds from a Wolfson Royal Society Merit Award. T.M.H. is supported by grants R01AI118985 and R01GM117424. A.E.I.P. and G.J.G. received funding from the European Union FP6 (INNOCHEM, grant number LSHB-CT-2005-518167) and from the European Union Seventh Framework Programme (FP7-2007-2013) under grant agreement HEALTH-F4-2011-281608 (TIMER).
Glasgow Author(s) Enlighten ID:Graham, Professor Gerard
Authors: Graham, G. J., Handel, T. M., and Proudfoot, A. E.I.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Trends in Immunology
ISSN (Online):1471-4981
Published Online:18 April 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Trends in Immunology 40(6):472-481
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
681091The ACKR2-CCR2 axis in development and diseaseGerard GrahamMedical Research Council (MRC)MR/M019764/1III -IMMUNOLOGY
600961Dissecting the chemokine basis for the orchestration of the in vivo inflammatory responseGerard GrahamWellcome Trust (WELLCOTR)099251/Z/12/ZIII -IMMUNOLOGY