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26.04.2019 | ACUTE LUNG INJURY

Inter-α-inhibitor Ameliorates Endothelial Inflammation in Sepsis

verfasst von: Vandy P. Stober, Yow-Pin Lim, Steven Opal, Lisheng Zhuo, Koji Kimata, Stavros Garantziotis

Erschienen in: Lung | Ausgabe 3/2019

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Abstract

Purpose

Vascular endothelial cells demonstrate severe injury in sepsis, and a reduction in endothelial inflammation would be beneficial. Inter-α-Inhibitor (IαI) is a family of abundant plasma proteins with anti-inflammatory properties and has been investigated in human and animal sepsis with encouraging results. We hypothesized that IαI may protect endothelia from sepsis-related inflammation.

Methods

IαI-deficient or sufficient mice were treated with endotoxin or underwent complement-induced lung injury. VCAM-1 and ICAM-1 expression was measured in blood and lung as marker of endothelial activation. Human endothelia were exposed to activated complement C5a with or without IαI. Blood from human sepsis patients was examined for VCAM-1 and ICAM-1 and levels were correlated with blood levels of IαI.

Results

IαI-deficient mice showed increased endothelial activation in endotoxin/sepsis- and complement-induced lung injury models. In vitro, levels of endothelial pro-inflammatory cytokines and cell growth factors induced by activated complement C5a were significantly decreased in the presence of IαI. This effect was associated with decreased ERK and NFκB activation. IαI levels were inversely associated with VCAM-1 and ICAM-1 levels in a human sepsis cohort.

Conclusions

IαI ameliorates endothelial inflammation and may be beneficial as a treatment of sepsis.

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Titel: Inter-α-inhibitor Ameliorates Endothelial Inflammation in Sepsis
verfasst von: Vandy P. Stober
Yow-Pin Lim
Steven Opal
Lisheng Zhuo
Koji Kimata
Stavros Garantziotis
Publikationsdatum: 26.04.2019
Verlag: Springer US
Erschienen in: Lung / Ausgabe 3/2019
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-019-00228-1

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Inter-α-inhibitor Ameliorates Endothelial Inflammation in Sepsis

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