Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration

Maurizio Brigotti, Pier Luigi Tazzari, Elisa Ravanelli, Domenica Carnicelli, Stefania Barbieri, Laura Rocchi, Valentina Arfilli, Gaia Scavia, Francesca Ricci, Andrea Bontadini, Roberta R. Alfieri, Pier Giorgio Petronini, Carmine Pecoraro, Alberto E. Tozzi, Alfredo Caprioli

Research output: Contribution to journalArticle

Abstract

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 con-firm 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.

Original languageEnglish
Pages (from-to)201-210
Number of pages10
JournalJournal of Leukocyte Biology
Volume88
Issue number1
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Degranulation
  • Endothelial cells
  • Hemolytic uremic syndrome
  • Polymorphonuclear leukocytes
  • Proinflammatory cytokine

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Fingerprint Dive into the research topics of 'Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration'. Together they form a unique fingerprint.

Cite this