Role of sCD40L in the pathogenesis of Hemolytic Uremic Syndrome (HUS).

ABREY-RECALDE, MARIA JIMENA; AMARAL, MARIA MARTA; ALVAREZ, ROMINA; ALBERTO, F; MEJIAS, MARIA PILAR; RAMOS, MARIA VICTORIA; FERNANDEZ BRANDO, ROMINA J; EXENI, RAMON; ALCONCHER, LAURA; PALERMO, MARINA SANDRA

Boston

Congreso; 9th International Symposium on Shiga Toxin (Verocytotin)-Producing Escherichia coli Infections . VTEC2015; 2015

Role of sCD40L in the pathogenesis of Hemolytic Uremic Syndrome (HUS).1Abrey-Recalde MJ, 2Amaral MM, 2Alvarez R, 1Alberto F, 1Mejías MP, 1Ramos MV, 1Fernandez-Brando RJ, 3Exeni R, 4Alconcher L, 1Palermo MS. 1Instituto de Medicina Experimental (IMEX), CONICET, Academia Nacional de Medicina. Bs As, Argentina.2Laboratorio de Fisiopatogenia, Departamento de Fisiología, Facultad de Medicina, UBA, Argentina.3Departamento de Nefrología, Hospital Municipal del Niño, San Justo. Pcia de Bs As, Argentina4Unidad de Nefrourología Infantil. Hospital Dr. José Penna, Bahía Blanca, Pcia de Bs As, ArgentinaIntroduction:Shiga-toxin (Stx) induces endothelial damage that leads to platelet activation. Activated platelets expose CD40L at surface, which is cleaved generating the soluble product (sCD40L).sCD40L-CD40 interaction enhances monocyte Tissue Factor (TF) expression, contributing to prothrombotic state. Furthermore, oxidative imbalance induced by Stx could enhance sCD40L through platelet activation. The aim of this work was to determine whether sCD40L are elevated during HUS and mediates Monocyte-procoagulant activity. Therefore, we evaluated if antioxidant N-Acetyl-Cisteine(NAC) prevents sCD40L releaseMaterial&Methods: Supernatants from culture of endothelial cells (E), with or without Stx(S), platelets (P), and NAC were collected. The treatments were: 1:E, 2:E+P, 3:E+S, 4:E+S+P, 5:E+S+P+NAC. sCD40L levels in supernatants and plasma (from HUS grade1-2 (HUS1-2), HUS grade 3 (HUS3)or healthy controls (HC)), were determined by ELISA.Control monocytes were incubated in presence of plasma of the same clinical groups depleted or not of sCD40L, and its TF expression was measured by Flow Cytometry Results:sCD40L (ng/ml, MEAN±SEM): Plasma: HC=1.48±0.27, HUS1-2=3.72±0.76*, HUS3=1.48±0.41 (*p