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Neutrophil Extracellular Traps Contribute To Endothelial Barrier Dysfunction During Sepsis
Author(s) -
Meegan Jamie E,
Beard Richard S,
Yang Xiaoyuan,
Reynolds Jason J,
Coleman Danielle C,
Jannaway Melanie,
Yuan Sarah Y
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.679.1
Subject(s) - neutrophil extracellular traps , adherens junction , microbiology and biotechnology , myeloperoxidase , intravital microscopy , endothelial dysfunction , inflammation , tight junction , barrier function , endothelium , endothelial stem cell , paracellular transport , biology , microcirculation , immunology , chemistry , medicine , cell , biochemistry , cadherin , endocrinology , in vitro , permeability (electromagnetism) , membrane
Neutrophil extracellular traps (NETs) are DNA‐webs containing histones and granular enzymes produced by neutrophils during host defense against infection. It is becoming increasingly apparent that circulating NETs exacerbate tissue injury associated with inflammation. The purpose of this study was to determine the effects of NETs on endothelial barrier function. We identified increased markers of NETs in the lung and plasma of mice subjected to polymicrobial septic injury induced by cecal ligation and puncture. In an intravital microscopic analysis of microcirculation, NETs were found in mesenteric microvessels in response to fMLP stimulation. In cultured endothelial cell monolayers, treatment with NETs produced by activated human neutrophils induced barrier dysfunction as indicated by reduced transendothelial electrical resistance and increased albumin transendothelial flux. Exogenous histones produced a similar effect on barrier dysfunction. Immunofluorescence confocal microscopy indicates the involvement of conformational changes in adherens junction proteins VE‐cadherin and β‐catenin as a potential mechanism underlying NET‐induced barrier dysfunction. Furthermore, myosin light chain phosphorylation in endothelial cells was observed after NET stimulation, supporting the involvement of cytoskeleton response in this process. Taken together, the data suggest NETs may contribute to endothelial barrier dysfunction during inflammatory response associated with neutrophil activation. Support or Funding Information This work is supported by NIH RO1s HL126646, HL070752, and GM097270.