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

ABREY RECALDE, MARIA; ALVAREZ, ROMINA; ALBERTO, FABIANA; MEJIAS, MARIA; RAMOS, MARIA; FERNANDEZ BRANDO, ROMINA; BRUBALLA, ANDREA; EXENI, RAMON; ALCONCHER, LAURA; IBARRA, CRISTINA; AMARAL, MARÍA; PALERMO, MARINA

Toxins

Basel : MDPI

Lugar: Basel; Año: 2017 vol. 9

Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrheaassociatedhemolytic uremic syndrome (HUS), which is characterized by the obstruction of renalmicrovasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generatedby Stx induces platelet activation, contributing to thrombus formation. Moreover, activated plateletsrelease soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggeringthe release of reactive oxidative species (ROS) on various cellular types. The aim of this workwas to determine if the interaction between the oxidative response and platelet-derived sCD40L,as consequence of Stx-induced endothelium damage, participates in the pathogenic mechanismduring HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets toadhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels ofsCD40L were released to the medium. The release of sCD40L by activated platelets was inhibitedby antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUSpatients, which were also able to trigger the respiratory burst in monocytes in a sCD40L-dependentmanner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocallystimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerularocclusion and the microangiopathic lesions