Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 17 August 2017 / Approved: 18 August 2017 / Online: 18 August 2017 (11:46:11 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Toxins 2017, 9, 331
DOI: 10.3390/toxins9110331

Abstract

Shiga toxin (Stx) produced by Escherichia coli is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by 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 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.

Subject Areas

hemolytic uremic syndrome; oxidative stress; blood platelets; shiga toxin 2; CD40L

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