L-selectin regulates human neutrophil transendothelial migration.

Autores de INCLIVA

• 

  María Jesús Sanz Ferrando

  Autor

Participantes ajenos a INCLIVA

• Rahman, Izajur
• Collado Sanchez, Aida
• Davies, Jessica
• Rzeniewicz, Karolina
• Abukscem, Sarah
• Joachim, Justin
• Hoskins Green, Hannah L
• Killock, David
• Charras, Guillaume
• Parsons, Maddy
• Ivetic, Aleksandar

Grupos y Plataformas de I+D+i

• Grupo de Investigación en Inflamación

  

  Established Co-IP Researcher

  Laura Piqueras Ruiz

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-1ß-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.

Keywords

• Diapedesis; JNK; PECAM-1; Transmigration; p38 MAPK