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L-selectin regulates human neutrophil transendothelial migration

Rahman, I; Sánchez, AC; Davies, J; Rzeniewicz, K; Abukscem, S; Joachim, J; Green, HLH; ... Ivetic, A; + view all (2021) L-selectin regulates human neutrophil transendothelial migration. Journal of Cell Science 10.1242/jcs.250340. (In press). Green open access

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Abstract

The migration of circulating neutrophils towards damage/infected tissue is absolutely critical to the inflammatory response. L-selectin is a cell adhesion molecule abundantly expressed on circulating neutrophils. For over two decades, neutrophil L-selectin has been assigned the exclusive role of supporting tethering and rolling - the initial stages of the multi-step adhesion cascade. Here, we provide direct evidence for L-selectin contributing to neutrophil transendothelial migration (TEM). We show that L-selectin co-clusters with PECAM-1 - a well-characterised cell adhesion molecule involved in regulating neutrophil TEM. This co-clustering behaviour occurs specifically during TEM, which serves to augment ectodomain shedding of L-selectin and expedite the time taken for TEM (TTT) to complete. Blocking PECAM-1 signalling (through mutation of its cytoplasmic tail), PECAM-1-dependent adhesion, or L-selectin shedding, led to a significant delay in the TTT. Finally, we show that co-clustering of L-selectin with PECAM-1 occurs specifically across TNF-α- but not IL-1β-activated endothelial monolayers - implying unique adhesion interactomes forming in a cytokine-specific manner. To our knowledge, this is the first report to implicate a non-canonical role for L-selectin in regulating neutrophil TEM.

Type: Article
Title: L-selectin regulates human neutrophil transendothelial migration
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/jcs.250340
Publisher version: https://doi.org/10.1242/jcs.250340
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Diapedesis, JNK, PECAM-1, Transmigration, p38 MAPK
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > London Centre for Nanotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10119013
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