Oligomerized, filamentous surface presentation of RANTES/CCL5 on vascular endothelial cells

Scientific Reports
Inger ØynebråtenGuttorm Haraldsen

Abstract

Vascular endothelial cells present luminal chemokines that arrest rolling leukocytes by activating integrins. It appears that several chemokines must form higher-order oligomers to elicit proper in vivo effects, as mutants restricted to forming dimers have lost the ability to recruit leukocytes to sites of inflammation. Here, we show for the first time that the chemokine RANTES/CCL5 binds to the surface of human endothelial cells in a regular filamentous pattern. Furthermore, the filaments bound to the surface in a heparan sulfate-dependent manner. By electron microscopy we observed labeling for RANTES on membrane projections as well as on the remaining plasma membrane. Mutant constructs of RANTES restricted either in binding to heparin, or in forming dimers or tetramers, appeared either in a granular, non-filamentous pattern or were not detectable on the cell surface. The RANTES filaments were also present after exposure to flow, suggesting that they can be present in vivo. Taken together with the lacking in vivo or in vitro effects of RANTES mutants, we suggest that the filamentous structures of RANTES may be of physiological importance in leukocyte recruitment.

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Citations

Apr 14, 2016·International Journal of Molecular Sciences·Maskomani SilambarasanKandiah Jeyaseelan
Apr 20, 2016·Proceedings of the National Academy of Sciences of the United States of America·Wenguang G LiangWei-Jen Tang
Aug 10, 2019·BioMed Research International·Olga M Koper-LenkiewiczVioletta Dymicka-Piekarska
Feb 14, 2021·Neurobiology of Aging·Eduardo Frías-AnayaIgnacio A Romero
Aug 3, 2020·Life Sciences·Gerwyn MorrisMichael Berk
Oct 24, 2020·Life Sciences·Gerwyn MorrisMichael Berk
Jun 30, 2021·Cytokine & Growth Factor Reviews·Ni ZhaoLi-Li Xu
Jul 25, 2021·International Journal of Molecular Sciences·Annemiek DickhoutRory R Koenen

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Methods Mentioned

BETA
confocal microscopy
electron microscopy
ELISA
lavage
scanning electron microscopy
transfection

Software Mentioned

ImageJ
Adobe Photoshop
GraphPad Prism
RANTES

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