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Endothelial Cells Exhibit Two Waves of P-selectin Surface Aggregation Under Endotoxic and Oxidative Conditions

  • Nathaly Barrionuevo
  • Sebastian Gatica
  • Pedro Olivares
  • Claudio Cabello-Verrugio
  • Felipe SimonEmail author
Article

Abstract

Sepsis is a clinical syndrome characterized by the presence of circulating microbial endotoxins and oxidative stress. Endotoxin and oxidative stress activate endothelial cells via a convergent signaling pathway (TLR4/MyD88/PI3 K/PLCɣ/NF-B) that stimulates both the transcription of SELP gene (which encodes for human P-selectin) and the release of P-selectin from Weibel–Palade bodies (WPBs). However, time course pattern of P-selectin surface aggregation has not been established in endothelial cells under 24 h of endotoxic or oxidative stress. Our study shows that P-selectin has at least two waves of aggregation at the cell surface: one 10 min and the other 12 h after endotoxic or oxidative stress. The first wave depends exclusively on WPB delivery to the cell membrane, while the second depends on P-selectin translation machinery, ER–Golgi sorting, and WPB surface delivery. Understanding adhesion molecule dynamics in endothelial cells could provide further molecular insights to develop diagnostic or therapeutic tools to aid in the management of sepsis.

Keywords

Adhesion molecules Endothelial cells Oxidative stress Endotoxemia Sepsis 

Abbreviations

ER

Endoplasmic reticulum

HUVEC

Human umbilical vein endothelial cell

IL

Interleukin

LPS

Lipopolysaccharide

NF–B

Nuclear factor–kappa B

PLCɣ

Phospholipase C gamma

ROS

Reactive oxygen species

TF

Tissue factor

TLR4

Toll-like receptor 4

TNF–⍺

Tumor necrosis factor–⍺

vWF

Von Willebrand Factor

WPB

Weibel–Palade bodies

Notes

Acknowledgements

This work was supported by research grants from Fondo Nacional de Desarrollo Científico y Tecnológico—FONDECYT 1161288, and 1161646, Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) PhD Scholarship 21171566, Millennium Institute on Immunology and Immunotherapy P09-016-F. Programa de Cooperación Científica ECOS-CONICYT C16S02. BASAL Grant CEDENNA FB0807. The Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD) is a Millennium Nucleus supported by the Iniciativa Científica Milenio of the Ministry of Economy, Development and Tourism (Chile).

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Authors and Affiliations

  1. 1.Facultad de Ciencias de la Vida, Universidad Andres BelloSantiagoChile
  2. 2.Millennium Institute on Immunology and ImmunotherapySantiagoChile
  3. 3.Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de ChileSantiagoChile
  4. 4.Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD), Universidad de ChileSantiagoChile

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