Induction of neutrophil extracellular traps in Shiga toxin-associated Hemolytic Uremic Syndrome

RAMOS MARÍA VICTORIA; MARIA PILAR MEJIAS; FLORENCIA SABBIONE; ROMINA JIMENA FERNANDEZ-BRANDO; ADRIANA PATRICIA SANTIAGO; MARIA MARTA AMARAL; RAMON EXENI; ANALIA TREVANI; MARINA SANDRA PALERMO

J Innate Immun

Karger

Lugar: Basel; Año: 2016 vol. 8 p. 400 - 411

Hemolytic Uremic Syndrome (HUS), a vascular disease characterized by hemolytic anemia, thrombocytopenia and acute renal failure is caused by enterohemorrhagic Shiga toxins (Stx)-producing bacteria, which mainly affect children. Besides Stx, the inflammatory response mediated by neutrophils (PMN) is essential to HUS evolution. PMN can release "neutrophil extracellular traps" (NETs) composed of DNA, histones and other proteins. Since NETs are involved in infectious and inflammatory diseases, the aim of this work was to investigate the contribution of NETs to HUS. Plasmas from HUS patients contained increased levels of circulating free-DNA and nucleosomes in comparison to healthy children plasmas. Neutrophils from HUS patients exhibited higher capacity to undergo spontaneous NETosis. NETs activated human glomerular endothelial cells stimulating secretion of the proinflammatory cytokines IL-6 and IL-8. Stx induced PMN activation as judged by its ability to trigger reactive oxygen species production, to increase CD11b and CD66b expression and to induce NETosis in PMN from healthy donors. During HUS, NETs could contribute to the inflammatory response and thrombosis in the microvasculature and thus, to renal failure. Intervention strategies to inhibit inflammatory mechanisms mediated by PMN, such as NETosis, could have potential therapeutic impact to ameliorate the severity of HUS