Endogenos glucocorticoids attenuate Shiga toxin 2-toxicity by modulation of neutrophil function in a murine model of Haemolytic Uremic Syndrome

GÓMEZ, SONIA; FERNÁNDEZ, GABRIELA; RUBEL, CAROLINA; ALVES ROSA, FERNANDA; BARRIONUEVO, PAULA; CAMERANO, GABRIELA VERÓNICA; ISTURIZ, MARTÍN; PALERMO, MARINA

Edinburgh

Congreso; 5th International Symposium on Shiga Toxin (Verocytotoxin) - Producing Escherichia Coli Infections; 2003

Hemolytic uremic syndrome (HUS) is caused by Shiga toxin (Stx) producing Escherichia coli. Clinical and experimental evidence suggest the participation of neutrophils (PMN) in this pathogenesis. Further, we have demonstrated in a murine model of HUS by an i.v. injection of Stx2 that glucocorticoids (GC) decrease Stx2 toxicity and that Stx2 induces GC receptor (GR) expression in PMN cells. Considering this, the objective of this study was to investigate the influence of endogenous GC on PMN function in Stx2-treated mice. We evaluated neutrophil function after Stx2 injection in the presence or absence of endogenous GC by treating mice with RU486 (specific GR antagonist). We evaluated zymozan-FITC phagocytosis, reactive oxygen intermediate (ROI) generation and apoptosis by flow cytometry in purified PMN obtained from mice treated with Stx2 or Stx2+Ru486 after different time points. The results are expressed as % increase ± SEM with respect to the control. Zymozan-FITC phagocytosis was significantly inhibited in Ru486+Stx2 treated mice with respect to Stx2 only at 24-post injection (71±3.5 vs. 82±3.0, p