Inhibition of Vascular Endothelial Cell Leak Following Escherichia coli Attachment in an Experimental Model of Sepsis

Critical Care Medicine
Tony M McHaleSteve W Kerrigan

Abstract

The vascular endothelium is a major target of sepsis-induced events, and endothelial activation accounts for much of the pathology of sepsis. Urinary tract infections and pneumonia caused by Escherichia coli are among of the most common infections causing sepsis in both community and hospital settings. Currently, there are no approved drugs on the market to treat the underlying pathophysiology of sepsis. The aim of this study is to elucidate the molecular mechanism by which E. coli induces endothelial injury as a result of attachment. Laboratory research using a hemodynamic perfusion ex vivo model. Research Laboratories of Royal College of Surgeons in Ireland and Beaumont Hospital. Ex vivo human vascular endothelial cells. Addition of αVβ3 antagonist, cilengitide. Clinical strains of E. coli isolated from patients with sepsis bound to sheared human endothelial cells under static and hemodynamic shear conditions. Binding was dependent on E. coli cell membrane protein outer membrane protein A attaching directly to endothelial cell integrin αVβ3. Attachment resulted in disturbances in endothelial barrier integrity, as determined by loss of tight junction protein staining, permeability changes, and ultimately cell death by apoptosi...Continue Reading

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Citations

May 20, 2020·Scientific Reports·Philipp NicolMichael Joner
Jun 16, 2019·Critical Care : the Official Journal of the Critical Care Forum·John J MariniJean-Louis Vincent
Jun 16, 2019·Critical Care : the Official Journal of the Critical Care Forum·Can Ince
Jul 21, 2020·Research and Practice in Thrombosis and Haemostasis·Robert AriensJohn Weisel
Aug 27, 2019·Frontiers in Immunology·Steven W KerriganDermot Cox
Feb 23, 2021·Journal of Intensive Care Medicine·Fei PengYi Yang
Oct 10, 2020·Drug Discovery Today·Danielle NaderSteven W Kerrigan

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