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 Simon

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)667-674
Number of pages8
JournalProtein Journal
Volume38
Issue number6
DOIs
Publication statusPublished - 1 Dec 2019

Keywords

  • Adhesion molecules
  • Endothelial cells
  • Endotoxemia
  • Oxidative stress
  • Sepsis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Bioengineering
  • Biochemistry
  • Organic Chemistry

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