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Toxins 2017, 9(11), 331; doi:10.3390/toxins9110331

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

1
Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, 1425 Buenos Aires, Argentina
2
Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica “Bernardo Houssay”, Facultad de Medicina-Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, 1121 Buenos Aires, Argentina
3
División Trombosis, Instituto de investigaciones Hematológicas “Mariano R. Castex”, Academia Nacional de Medicina, 1425 Buenos Aires, Argentina
4
Departamento de Nefrología, Hospital Municipal del Niño, San Justo, B1754FUD Provincia de Buenos Aires, Argentina
5
Unidad de Nefrourología Infantil. Hospital Interzonal General Dr. José Penna, Bahía Blanca, 8000 Provincia de Buenos Aires, Argentina
*
Author to whom correspondence should be addressed.
Academic Editors: Andreja Rajkovic and Gerald B. Koudelka
Received: 17 August 2017 / Revised: 29 September 2017 / Accepted: 15 October 2017 / Published: 25 October 2017
(This article belongs to the Collection Shiga Toxins)
View Full-Text   |   Download PDF [6522 KB, uploaded 25 October 2017]   |  

Abstract

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. View Full-Text
Keywords: hemolytic uremic syndrome; oxidative stress; blood platelets; Shiga toxin 2; CD40L hemolytic uremic syndrome; oxidative stress; blood platelets; Shiga toxin 2; CD40L
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Abrey Recalde, M.J.; Alvarez, R.S.; Alberto, F.; Mejias, M.P.; Ramos, M.V.; Fernandez Brando, R.J.; Bruballa, A.C.; Exeni, R.A.; Alconcher, L.; Ibarra, C.A.; Amaral, M.M.; Palermo, M.S. Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome. Toxins 2017, 9, 331.

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