Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis.
Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis.
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DOI：
10.1016/j.immuni.2018.09.018
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发表时间：
2018-12-18
期刊：
影响因子：
32.4
通讯作者：
Nourshargh S
中科院分区：
文献类型：
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作者：
Girbl T;Lenn T;Perez L;Rolas L;Barkaway A;Thiriot A;Del Fresno C;Lynam E;Hub E;Thelen M;Graham G;Alon R;Sancho D;von Andrian UH;Voisin MB;Rot A;Nourshargh S
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. The CXCR2 ligands CXCL1 and CXCL2 play distinct roles in neutrophil diapedesis Endothelial cell (EC)- and pericyte-derived CXCL1 mediate neutrophil crawling CXCL2 is neutrophil derived and is retained at EC junctions by ACKR1 ACKR1-CXCL2 axis is critical for unidirectional paracellular neutrophil TEM in vivo Girbl et al. find that sequential interactions with the chemokines CXCL1 and CXCL2 guide neutrophil crawling and subsequent migration through venular walls during inflammation. Transmigrating neutrophils promoted unidirectional luminal-to-abluminal migration by depositing CXCL2 on the chemokine receptor ACKR1 at endothelial junctions, providing a paradigm of self-guided migration.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
30.5
作者：
Duchene J;Novitzky-Basso I;Thiriot A;Casanova-Acebes M;Bianchini M;Etheridge SL;Hub E;Nitz K;Artinger K;Eller K;Caamaño J;Rülicke T;Moss P;Megens RTA;von Andrian UH;Hidalgo A;Weber C;Rot A
通讯作者：
Rot A
影响因子：
4.8
作者：
Rajagopal, Sudarshan;Bassoni, Daniel L.;Wehrman, Tom S.
通讯作者：
Wehrman, Tom S.
影响因子：
5.5
作者：
Armstrong, DA;Major, JA;Hamilton, TA
通讯作者：
Hamilton, TA
影响因子：
30.5
作者：
通讯作者：
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