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Blood Plasma Obtained From Severe Sepsis‐Patients Up‐regulates Pro‐inflammatory Phenotype in Human Cerebrovascular Endothelial Cells In Vitro
Author(s) -
Blom Christopher J,
Fraser Douglas D,
Martin Claudio,
Cepinskas Gediminas
Publication year - 2011
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.25.1_supplement.116.9
Subject(s) - sepsis , inflammation , stimulation , cytokine , vascular permeability , endothelial dysfunction , medicine , endothelial activation , tumor necrosis factor alpha , systemic inflammation , immunology , endothelium , in vitro , phenotype , encephalopathy , endothelial stem cell , chemistry , gene , biochemistry
The mechanisms of sepsis‐associated encephalopathy (SAE) are largely uninvestigated. It has been hypothesized that impaired function of cerebrovascular endothelium may play a key role in the development of SAE. Our recent findings indicate that Severe Sepsis in human patients results in an induction of systemic inflammation as assessed by the increase in pro‐inflammatory cytokine expression in blood plasma. In this study we employed human‐derived cerebrovascular endothelial cells (CVEC) and blood plasma obtained from either patients with Severe Sepsis (hSSP) or healthy controls (hNP) to assess the effects/mechanisms of hSSP‐plasma stimulation on CVEC activation/dysfunction. The obtained results indicate that stimulation of CVEC with hSSP (20% vol/vol) for 1hr results in CVEC activation (increased production of ROS; DHR123 oxidation) and activation of inflammation‐relevant transcription factor, NFκB (ELISA). Subsequently, stimulation of CVEC with hSSP for 4 or 24 hrs resulted in an increase in PMN rolling/adhesion to CVEC under conditions of flow (3dyn/cm 2 ) and an increase in CVEC permeability as assessed by a decrease in transendothelial electric resistance (TEER). Our findings indicate that CVEC challenged with hSSP induces an acute pro‐inflammatory phenotype and subsequent dysfunction (increased permeability), which in turn may directly contribute to the development of SAE. (IRF 08–10)