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 language | English |
|---|---|
| Pages (from-to) | 201-210 |
| Number of pages | 10 |
| Journal | Journal of Leukocyte Biology |
| Volume | 88 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2010 |
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Keywords
- Degranulation
- Endothelial cells
- Hemolytic uremic syndrome
- Polymorphonuclear leukocytes
- Proinflammatory cytokine
ASJC Scopus subject areas
- Cell Biology
- Immunology
Cite this
Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration. / Brigotti, Maurizio; Tazzari, Pier Luigi; Ravanelli, Elisa; Carnicelli, Domenica; Barbieri, Stefania; Rocchi, Laura; Arfilli, Valentina; Scavia, Gaia; Ricci, Francesca; Bontadini, Andrea; Alfieri, Roberta R.; Petronini, Pier Giorgio; Pecoraro, Carmine; Tozzi, Alberto E.; Caprioli, Alfredo.
In: Journal of Leukocyte Biology, Vol. 88, No. 1, 07.2010, p. 201-210.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration
AU - Brigotti, Maurizio
AU - Tazzari, Pier Luigi
AU - Ravanelli, Elisa
AU - Carnicelli, Domenica
AU - Barbieri, Stefania
AU - Rocchi, Laura
AU - Arfilli, Valentina
AU - Scavia, Gaia
AU - Ricci, Francesca
AU - Bontadini, Andrea
AU - Alfieri, Roberta R.
AU - Petronini, Pier Giorgio
AU - Pecoraro, Carmine
AU - Tozzi, Alberto E.
AU - Caprioli, Alfredo
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - Degranulation
KW - Endothelial cells
KW - Hemolytic uremic syndrome
KW - Polymorphonuclear leukocytes
KW - Proinflammatory cytokine
UR - http://www.scopus.com/inward/record.url?scp=77954662966&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954662966&partnerID=8YFLogxK
U2 - 10.1189/jlb.0709475
DO - 10.1189/jlb.0709475
M3 - Article
C2 - 20371598
AN - SCOPUS:77954662966
VL - 88
SP - 201
EP - 210
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 1
ER -