Involvement of neutrophil extracellular traps in Hemolytic Uremic Syndrome

RAMOS M V; MEJÍAS M P; SABBIONE M F; ABREY RECALDE M J; FERNANDEZ BRANDO R J; TREVANI A; PALERMO MS.

Los Cocos

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Hemolytic Uremic Syndrome (HUS), a vascular disease characterized by hemolityc anemia, thrombocitopenia and acute renal failure is caused by enterohemorraghic Shiga toxins (Stx)-producing bacteria. Besides Stx, inflammatory response mediated by neutrophils (PMN) is essential to HUS evolution. PMN perform their function by engulfing microorganisms and degrading them by various molecules, and also release lytic enzymes that destroy extracellular pathogens. Moreover, they release structures called neutrophil extracellular traps (NETs) that can trap and kill microbes. These structures are composed of nuclear chromatin, associated mainly with nuclear histones and many granular antimicrobial proteins, as well as some cytoplasmic proteins. The large amounts of superoxide produced by the membrane-associated NADPH oxidase in PMN have a central role in the destruction of invading pathogens as well as in the resolution of inflammation. It is reported that formation of NETs by activated PMN requires NADPH-oxidase-mediated superoxide production. Experimental evidence suggests that NETs participate in pathogenesis of autoimmune and inflammatory disorders, and was proposed to be involved in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. Our hypothesis is that PMN could go under NETosis in inflammatory conditions developed during HUS. This could lead to deposition of NETs over renal endothelium contributing to renal damage and the microangiopathy in HUS evolution.