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Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induce...

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Autores principales: Abrey Recalde, Maria J., Alvarez, Romina S., Alberto, Fabiana, Mejias, Maria P., Ramos, Maria V., Fernandez Brando, Romina J., Bruballa, Andrea C., Exeni, Ramon A., Alconcher, Laura, Ibarra, Cristina A., Amaral, María M., Palermo, Marina S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705951/
https://www.ncbi.nlm.nih.gov/pubmed/29068360
http://dx.doi.org/10.3390/toxins9110331
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author Abrey Recalde, Maria J.
Alvarez, Romina S.
Alberto, Fabiana
Mejias, Maria P.
Ramos, Maria V.
Fernandez Brando, Romina J.
Bruballa, Andrea C.
Exeni, Ramon A.
Alconcher, Laura
Ibarra, Cristina A.
Amaral, María M.
Palermo, Marina S.
author_facet Abrey Recalde, Maria J.
Alvarez, Romina S.
Alberto, Fabiana
Mejias, Maria P.
Ramos, Maria V.
Fernandez Brando, Romina J.
Bruballa, Andrea C.
Exeni, Ramon A.
Alconcher, Laura
Ibarra, Cristina A.
Amaral, María M.
Palermo, Marina S.
author_sort Abrey Recalde, Maria J.
collection PubMed
description Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L, as consequence of Stx-induced endothelium damage, participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.
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spelling pubmed-57059512017-12-04 Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome Abrey Recalde, Maria J. Alvarez, Romina S. Alberto, Fabiana Mejias, Maria P. Ramos, Maria V. Fernandez Brando, Romina J. Bruballa, Andrea C. Exeni, Ramon A. Alconcher, Laura Ibarra, Cristina A. Amaral, María M. Palermo, Marina S. Toxins (Basel) Article Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L, as consequence of Stx-induced endothelium damage, participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions. MDPI 2017-10-25 /pmc/articles/PMC5705951/ /pubmed/29068360 http://dx.doi.org/10.3390/toxins9110331 Text en © 2017 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Abrey Recalde, Maria J.
Alvarez, Romina S.
Alberto, Fabiana
Mejias, Maria P.
Ramos, Maria V.
Fernandez Brando, Romina J.
Bruballa, Andrea C.
Exeni, Ramon A.
Alconcher, Laura
Ibarra, Cristina A.
Amaral, María M.
Palermo, Marina S.
Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome
title Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome
title_full Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome
title_fullStr Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome
title_full_unstemmed Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome
title_short Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome
title_sort soluble cd40 ligand and oxidative response are reciprocally stimulated during shiga toxin-associated hemolytic uremic syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705951/
https://www.ncbi.nlm.nih.gov/pubmed/29068360
http://dx.doi.org/10.3390/toxins9110331
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