Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration

Journal of Leukocyte Biology

Andrea Bontadini⁵  Domenica Carnicelli³  Maurizio Brigotti³  Gaia Scavia⁴  Pier Giorgio Petronini²  Valentina Arfilli³  Alberto E. Tozzi¹  Francesca Ricci⁵  Alfredo Caprioli⁴  Laura Rocchi³  Roberta R. Alfieri²  Pier Luigi Tazzari⁵  Stefania Barbieri³  Carmine Pecoraro⁶  Elisa Ravanelli³ 

[1] Ospedale Pediatrico Bambino Gesù, Rome, Italy Ospedale Pediatrico Bambino Gesù, Rome, Italy Ospedale Pediatrico Bambino Gesù, Rome, ItalyDipartimento di Medicina Sperimentale, Sezione di Patologia Molecolare e Immunologia, Università di Parma, Parma, Italy; Dipartimento di Medicina Sperimentale, Sezione di Patologia Molecolare e Immunologia, Università di Parma, Parma, Italy; Dipartimento di Medicina Sperimentale, Sezione di Patologia Molecolare e Immunologia, Università di Parma, Parma, Italy;Dipartimento di Patologia Sperimentale, Università di Bologna, Italy; Dipartimento di Patologia Sperimentale, Università di Bologna, Italy; Dipartimento di Patologia Sperimentale, Università di Bologna, Italy;Istituto Superiore di Sanità, Rome, Italy; Istituto Superiore di Sanità, Rome, Italy; Istituto Superiore di Sanità, Rome, Italy;Servizio di Immunoematologia e Trasfusionale, Ospedale S. Orsola-Malpighi, Bologna, Italy; Servizio di Immunoematologia e Trasfusionale, Ospedale S. Orsola-Malpighi, Bologna, Italy; Servizio di Immunoematologia e Trasfusionale, Ospedale S. Orsola-Malpighi, Bologna, Italy;;Ospedale Santobono, Naples, Italy; and Ospedale Santobono, Naples, Italy; and Ospedale Santobono, Naples, Italy; and

关键词: hemolytic uremic syndrome;    polymorphonuclear leukocytes;    endothelial cells;    proinflammatory cytokine;    degranulation;   

DOI  :  10.1189/jlb.0709475

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The endothelial damage induced by Stx represents the main pathogenic event in the HUS associated with STEC infections in humans. Stx, released in the gut by bacteria, enter the bloodstream and are targeted to renal endothelia. The role of PMN as a toxin carrier has been the object of controversy. In this paper, we confirm the binding of Stx1 to PMN, also showing its degranulating effects on full-loaded leukocytes, and support the carrier role of PMN by using a two-chamber transmigration device, in which PMN, loaded in vitro with different amounts of Stx1, transmigrated through confluent monolayers of endothelial cells, mimicking the toxin-induced renal endothelial injury. Stx1 was transferred during PMN transmigration, impairing protein synthesis and triggering production of proinflammatory cytokines in endothelial cells. PMN, carrying low toxin amounts, induced the release of high levels of cytokines in viable endothelial cells, whereas cytokine production was blocked in cells challenged with PMN fully loaded with Stx as a result of an almost total impairment of translation and of the activation of the apoptotic program. In agreement with previous unexplained observations in animal models, the results obtained with our experimental setting suggest that a self-amplifying circle triggered by low doses of toxin may lead to the production of proinflammatory mediators of renal damage in HUS.

【 授权许可】

Unknown