Inter-α-inhibitor Ameliorates Endothelial Inflammation in Sepsis
| Autor: | Lisheng Zhuo, Koji Kimata, Yow-Pin Lim, Vandy P. Stober, Stavros Garantziotis, Steven M. Opal |
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| Rok vydání: | 2019 |
| Předmět: |
Pulmonary and Respiratory Medicine
MAPK/ERK pathway Lipopolysaccharide MAP Kinase Signaling System Acute Lung Injury Vascular Cell Adhesion Molecule-1 Complement C5a Inflammation In Vitro Techniques Lung injury Article Sepsis Endothelial activation Mice chemistry.chemical_compound Alpha-Globulins Human Umbilical Vein Endothelial Cells medicine Animals Humans Lung business.industry NF-kappa B Endothelial Cells Intercellular Adhesion Molecule-1 medicine.disease Blood proteins Endotoxins Disease Models Animal chemistry Immunology Endothelium Vascular medicine.symptom E-Selectin business |
| Zdroj: | Lung |
| ISSN: | 1432-1750 0341-2040 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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