2026-04-29T04:09:05Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/71432024-09-27T08:55:14Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Girbl, Tamara
author
Lenn, Tchern
author
Perez, Lorena
author
Rolas, Loïc
author
Barkaway, Anna
author
Thiriot, Aude
author
del Fresno, Carlos
author
Lynam, Eleanor
author
Hub, Elin
author
Thelen, Marcus
author
Graham, Gerard
author
Alon, Ronen
author
Sancho, David
author
von Andrian, Ulrich H
author
Voisin, Mathieu-Benoit
author
Rot, Antal
author
Nourshargh, Sussan
funder
National Institutes of Health (Estados Unidos)
funder
Japan Foundation for Pediatric Research
funder
British Heart Foundation
funder
Unión Europea. Comisión Europea
funder
Wellcome Trust
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Swiss National Science Foundation
2019-02-07T13:59:58Z
2019-02-07T13:59:58Z
2018-12-18
Immunity. 2018; 49(6):1062-76
1074-7613
http://hdl.handle.net/20.500.12105/7143
30446388
10.1016/j.immuni.2018.09.018
1097-4180
Immunity
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.
eng
ACKR1
CXCR2
Chemokines
Endothelium
Extravasation
Inflammation
Neutrophils
Pericytes
Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis
journal article
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DistinctCompartmentalizationOfTheChemokinesCXCL1_2018.pdf.txt
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