L-selectin regulates human neutrophil transendothelial migration

Alex Ivetic; Izajur Rahman; Aida  Collado Sánchez; Jessica Davies; Karolina Rzeniewicz; Sarah Abukscem; Justin Joachim; Hannah Green; David Killock; Maria Jesus  Sanz; Guillaume Charras; Madeline Parsons

L-selectin regulates human neutrophil transendothelial migration

Alex Ivetic, Izajur Rahman, Aida Collado Sánchez, Jessica Davies, Karolina Rzeniewicz, Sarah Abukscem, Justin Joachim, Hannah Green, David Killock, Maria Jesus Sanz, Guillaume Charras, Madeline Parsons

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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.

Original language	English
Journal	Journal of Cell Science
Publication status	Published - 8 Feb 2021

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Rahman et al 2021Accepted author manuscript, 4.29 MBLicence: CC BY

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@article{8b2dae4e141149f3a7fa3c91a6adaf68,

title = "L-selectin regulates human neutrophil transendothelial migration",

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.",

author = "Alex Ivetic and Izajur Rahman and {Collado S{\'a}nchez}, Aida and Jessica Davies and Karolina Rzeniewicz and Sarah Abukscem and Justin Joachim and Hannah Green and David Killock and Sanz, {Maria Jesus} and Guillaume Charras and Madeline Parsons",

year = "2021",

month = feb,

day = "8",

language = "English",

journal = "Journal of Cell Science",

issn = "0021-9533",

publisher = "Company of Biologists Ltd",

}

TY - JOUR

T1 - L-selectin regulates human neutrophil transendothelial migration

AU - Ivetic, Alex

AU - Rahman, Izajur

AU - Collado Sánchez, Aida

AU - Davies, Jessica

AU - Rzeniewicz, Karolina

AU - Abukscem, Sarah

AU - Joachim, Justin

AU - Green, Hannah

AU - Killock, David

AU - Sanz, Maria Jesus

AU - Charras, Guillaume

AU - Parsons, Madeline

PY - 2021/2/8

Y1 - 2021/2/8

N2 - 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.

AB - 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.

M3 - Article

SN - 0021-9533

JO - Journal of Cell Science

JF - Journal of Cell Science

ER -

L-selectin regulates human neutrophil transendothelial migration

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