title: Induction of Neutrophil Extracellular Traps in Shiga Toxin-Associated Hemolytic Uremic Syndrome.
abstract: Hemolytic uremic syndrome (HUS), a vascular disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure, is caused by enterohemorrhagic Shiga toxin (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 (NET) composed of DNA, histones, and other proteins. Since NET are involved in infectious and inflammatory diseases, the aim of this work was to investigate the contribution of NET to HUS. Plasma from HUS patients contained increased levels of circulating free-DNA and nucleosomes in comparison to plasma from healthy children. Neutrophils from HUS patients exhibited a greater capacity to undergo spontaneous NETosis. NET 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, increase CD11b and CD66b expression, and induce NETosis in PMN from healthy donors. During HUS, NET can 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 a potential therapeutic impact towards amelioration of the severity of HUS.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Ramos
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Mejias
authors.forename: Florencia
authors.initials: F
authors.lastname: Sabbione
authors.forename: Romina Jimena
authors.initials: RJ
authors.lastname: Fernandez-Brando
authors.forename: Adriana Patricia
authors.initials: AP
authors.lastname: Santiago
authors.forename: Maria Marta
authors.initials: MM
authors.lastname: Amaral
authors.forename: Ramon
authors.initials: R
authors.lastname: Exeni
authors.forename: Analia Silvina
authors.initials: AS
authors.lastname: Trevani
authors.forename: Marina Sandra
authors.initials: MS
authors.lastname: Palermo
mesh_terms: D058186:Acute Kidney Injury; D000743:Anemia, Hemolytic; D017209:Apoptosis; D001424:Bacterial Infections / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D042783:Endothelial Cells / Q000276:immunology*; D065206:Extracellular Traps / Q000276:immunology*; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D022621:Shiga Toxin / Q000276:immunology*; D013921:Thrombocytopenia
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D022621:Shiga Toxin