2026-04-29T04:09:04Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/71432024-09-27T08:55:14Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2018-12-18 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. 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 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