Izajur Rahman, Aida Collado Sánchez, Jessica Davies, Karolina Rzeniewicz, Sarah Abukscem, Justin Joachim, Hannah L Hoskins Green, David Killock, Maria Jesus Sanz, Guillaume Charras, Maddy Parsons, Aleksandar Ivetic
Journal of cell science 2021 Feb 08The 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-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. © 2021. Published by The Company of Biologists Ltd.
Izajur Rahman, Aida Collado Sánchez, Jessica Davies, Karolina Rzeniewicz, Sarah Abukscem, Justin Joachim, Hannah L Hoskins Green, David Killock, Maria Jesus Sanz, Guillaume Charras, Maddy Parsons, Aleksandar Ivetic. L-selectin regulates human neutrophil transendothelial migration. Journal of cell science. 2021 Feb 08;134(3)
PMID: 33408247
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