L-selectin regulates human neutrophil transendothelial migration
Open Access
- 1 February 2021
- journal article
- research article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 134 (3)
- https://doi.org/10.1242/jcs.250340
Abstract
The migration of circulating neutrophils towards damaged or 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, leads to a significant delay in the TTT. Finally, we show that co-clustering of L-selectin with PECAM-1 occurs specifically across TNF- but not IL-1 beta-activated endothelial monolayers - implying unique adhesion interactomes forming in a cytokine-specificmanner. To our knowledge, this is the first report to implicate a non-canonical role for L-selectin in regulating neutrophil TEM.Funding Information
- European Union
- King's College London
- Biotechnology and Biological Sciences Research Council (BB/J014567, BB/M009513/1)
- British Heart Foundation (FS/18/60/3418)
- Centre of Research Excellence (RE/13/2/30182)
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