Cytoprotective and Antioxidant Effects of Steen Solution on Human Lung Spheroids and Human Endothelial Cells

Autor: Roberto Carnevale, Giorgio Mangino, Mohsen Ibrahim, Luca Fianchini, Isotta Chimenti, Giacomo Frati, Sebastiano Sciarretta, Camilla Siciliano, Cristina Nocella, Francesca Pagano, E. De Falco
Rok vydání: 2016
Předmět:
basic research science
cellular biology
ischemia reperfusion injury
lung transplantation/pulmonology
molecular biology
organ perfusion and preservation
signaling
signaling pathways
tissue injury and repair
translational research
science
0301 basic medicine
Male
030204 cardiovascular system & hematology
Pharmacology
Umbilical vein
Antioxidants
0302 clinical medicine
Immunology and Allergy
Medicine
Pharmacology (medical)
Lung
Cells
Cultured
chemistry.chemical_classification
NADPH oxidase
biology
Organ Preservation
medicine.anatomical_structure
Reperfusion Injury
NADPH Oxidase 2
cardiovascular system
Female
Adult
Adolescent
Organ Preservation Solutions
Proinflammatory cytokine
03 medical and health sciences
Young Adult
Downregulation and upregulation
Spheroids
Cellular
Human Umbilical Vein Endothelial Cells
Humans
Progenitor cell
Transplantation
Reactive oxygen species
business.industry
030104 developmental biology
chemistry
Cytoprotection
biology.protein
Isotonic Solutions
business
Reactive Oxygen Species
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 17(7)
ISSN: 1600-6143
Popis: Respiratory diseases represent a major healthcare burden worldwide. Lung transplantation (LTx) is the "gold standard" for end-stage patients, strongly limited by shortage of available/suitable donor lungs. Normothermic ex vivo lung perfusion (EVLP) has significantly increased the number of lungs suitable for transplantation. Steen solution is used for EVLP, but the mechanisms involved in its beneficial properties remain to be clarified. We investigated the effects of Steen solution in an in vitro protocol of cold starvation and normothermic recovery on human lung spheroids, named pneumospheres (PSs), containing epithelial/basal cells, and on endothelial human umbilical vein endothelial cells (HUVEC). Steen solution significantly preserved the viability of PSs, reduced reactive oxygen species (ROS) release by PSs and HUVECs, decreased NADPH-oxidase (NOX) activity in PSs, and reduced inflammatory cytokines expression levels in HUVECs. Steen solution was able to specifically reduce NADPH oxidase 2 (NOX2) isoform activation, particularly in PSs, as detected by soluble-NOX2 peptide and p47-phosphorylation. Interestingly, a specific NOX2 inhibitor could partly mimic the pro-survival effect of Steen on PSs. We provide the first evidence that Steen solution can preserve lung epithelial/progenitor cells viability partially through NOX2 downregulation, and exert antioxidant effects on parenchymal cells, with consequent ROS reduction. These results suggest that NOX2 inhibition might be an additional strategy to reduce cellular damage during LTx procedures.
Databáze: OpenAIRE
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