Girbl, T;
Lenn, T;
Perez, L;
Rolas, L;
Barkaway, A;
Thiriot, A;
Del Fresno, C;
... Nourshargh, S; + view all
(2018)
Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis.
Immunity
, 49
(6)
1062-1076.e6.
10.1016/j.immuni.2018.09.018.
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Abstract
Neutrophils require directional cues to navigate through the complex structure of venular walls and into inflamed tissues. Here we applied confocal intravital microscopy to analyze neutrophil emigration in cytokine-stimulated mouse cremaster muscles. We identified differential and non-redundant roles for the chemokines CXCL1 and CXCL2, governed by their distinct cellular sources. CXCL1 was produced mainly by TNF-stimulated endothelial cells (ECs) and pericytes and supported luminal and sub-EC neutrophil crawling. Conversely, neutrophils were the main producers of CXCL2, and this chemokine was critical for correct breaching of endothelial junctions. This pro-migratory activity of CXCL2 depended on the atypical chemokine receptor 1 (ACKR1), which is enriched within endothelial junctions. Transmigrating neutrophils promoted a self-guided migration response through EC junctions, creating a junctional chemokine "depot" in the form of ACKR1-presented CXCL2 that enabled efficient unidirectional luminal-to-abluminal migration. Thus, CXCL1 and CXCL2 act in a sequential manner to guide neutrophils through venular walls as governed by their distinct cellular sources.
| Type: | Article |
|---|---|
| Title: | Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.immuni.2018.09.018 |
| Publisher version: | https://doi.org/10.1016/j.immuni.2018.09.018 |
| Language: | English |
| Additional information: | © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
| Keywords: | ACKR1, CXCR2, chemokines, endothelium, extravasation, inflammation, neutrophils, pericytes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10065019 |
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