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In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells

Eryptosis is the stress-induced RBC (red blood cell) death mechanism. It is known that eryptosis is largely influenced by plasma and blood composition, and that it is accelerated in patients affected by chronic kidney disease (CKD). The aim of this study is to evaluate the eryptosis rate in healthy...

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Autores principales: Virzì, Grazia Maria, Mattiotti, Maria, Clementi, Anna, Milan Manani, Sabrina, Battaglia, Giovanni Giorgio, Ronco, Claudio, Zanella, Monica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501441/
https://www.ncbi.nlm.nih.gov/pubmed/36142976
http://dx.doi.org/10.3390/jcm11185329
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author Virzì, Grazia Maria
Mattiotti, Maria
Clementi, Anna
Milan Manani, Sabrina
Battaglia, Giovanni Giorgio
Ronco, Claudio
Zanella, Monica
author_facet Virzì, Grazia Maria
Mattiotti, Maria
Clementi, Anna
Milan Manani, Sabrina
Battaglia, Giovanni Giorgio
Ronco, Claudio
Zanella, Monica
author_sort Virzì, Grazia Maria
collection PubMed
description Eryptosis is the stress-induced RBC (red blood cell) death mechanism. It is known that eryptosis is largely influenced by plasma and blood composition, and that it is accelerated in patients affected by chronic kidney disease (CKD). The aim of this study is to evaluate the eryptosis rate in healthy RBCs treated with different concentration of IL-6, IL-1β, urea and p-cresol, comparable to plasmatic level of CKD patients, at different time points. We exposed healthy RBCs to increasing concentrations of IL-6, IL-1β, urea and p-cresol. Morphological markers of eryptosis (cell membrane scrambling, cell shrinkage and PS exposure at RBC surface) were evaluated by flow cytometric analyses. The cytotoxic effect of cytokines and uremic toxins were analyzed in vitro on healthy RBCs at 4, 8 and 24 h. Morphology of treated RBCs was dramatically deranged, and the average cell volume was significantly higher in RBCs exposed to higher concentration of all molecules (all, p < 0.001). Furthermore, healthy RBCs incubated with each molecules demonstrated a significant increase in eryptosis. Cytofluorimetric analysis of eryptosis highlighted significantly higher cell death rate in RBCs incubated with a higher concentration of both cytokines compared with RBCs incubated with a lower concentration (all, p < 0.05). In conclusion, our data show that cytokines and uremic toxins have a harmful effect on RBCs viability and trigger eryptosis. Further studies are necessary to validate these results in vivo and to associate abnormal eryptosis with cytokine levels in CKD patients. The eryptosis pathway could, moreover, become a new promising target for anemia management in CKD patients.
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spelling pubmed-95014412022-09-24 In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells Virzì, Grazia Maria Mattiotti, Maria Clementi, Anna Milan Manani, Sabrina Battaglia, Giovanni Giorgio Ronco, Claudio Zanella, Monica J Clin Med Article Eryptosis is the stress-induced RBC (red blood cell) death mechanism. It is known that eryptosis is largely influenced by plasma and blood composition, and that it is accelerated in patients affected by chronic kidney disease (CKD). The aim of this study is to evaluate the eryptosis rate in healthy RBCs treated with different concentration of IL-6, IL-1β, urea and p-cresol, comparable to plasmatic level of CKD patients, at different time points. We exposed healthy RBCs to increasing concentrations of IL-6, IL-1β, urea and p-cresol. Morphological markers of eryptosis (cell membrane scrambling, cell shrinkage and PS exposure at RBC surface) were evaluated by flow cytometric analyses. The cytotoxic effect of cytokines and uremic toxins were analyzed in vitro on healthy RBCs at 4, 8 and 24 h. Morphology of treated RBCs was dramatically deranged, and the average cell volume was significantly higher in RBCs exposed to higher concentration of all molecules (all, p < 0.001). Furthermore, healthy RBCs incubated with each molecules demonstrated a significant increase in eryptosis. Cytofluorimetric analysis of eryptosis highlighted significantly higher cell death rate in RBCs incubated with a higher concentration of both cytokines compared with RBCs incubated with a lower concentration (all, p < 0.05). In conclusion, our data show that cytokines and uremic toxins have a harmful effect on RBCs viability and trigger eryptosis. Further studies are necessary to validate these results in vivo and to associate abnormal eryptosis with cytokine levels in CKD patients. The eryptosis pathway could, moreover, become a new promising target for anemia management in CKD patients. MDPI 2022-09-10 /pmc/articles/PMC9501441/ /pubmed/36142976 http://dx.doi.org/10.3390/jcm11185329 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Virzì, Grazia Maria
Mattiotti, Maria
Clementi, Anna
Milan Manani, Sabrina
Battaglia, Giovanni Giorgio
Ronco, Claudio
Zanella, Monica
In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells
title In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells
title_full In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells
title_fullStr In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells
title_full_unstemmed In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells
title_short In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells
title_sort in vitro induction of eryptosis by uremic toxins and inflammation mediators in healthy red blood cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501441/
https://www.ncbi.nlm.nih.gov/pubmed/36142976
http://dx.doi.org/10.3390/jcm11185329
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