Shiga Toxin-2 Induces Neutrophilia and Neutrophil Activation in a Murine Model of Hemolytic Uremic Syndrome

Fernández, Gabriela; Rubel, Carolina; Dran, Graciela; Gómez, Sonia; Isturiz, Martı́n A.; Palermo, Marina S.

doi:10.1006/clim.2000.4862

Cited by 36 publications

(49 citation statements)

References 44 publications

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“…Interestingly, injection of purified Stx2 has also been shown to induce neutrophilia and neutrophil activation in a murine model of HUS (5). Thus, our findings provide a further example of the similarities between the effects of the two toxins in vivo.…”

Section: Vol 79 2011supporting

confidence: 60%

“…Stx1 has also been shown to block the activation and proliferation of lymphocytes (4,13). The similarities in the properties of SubAB and Stx are remarkable given the fact that the two AB 5 toxins are unrelated and have distinct host receptors, intracellular targets, and molecular mechanisms of action. The B subunit of SubAB mediates binding to Neu5Gc displayed on sialated glycoproteins (2), triggering clathrin-dependent internalization and retrograde transport via the Golgi complex to the ER lumen (3), where the proteolytic A subunit cleaves the essential Hsp70 family chaperone BiP (15).…”

Section: Vol 79 2011mentioning

confidence: 99%

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In Vivo Leukocyte Changes Induced by Escherichia coli Subtilase Cytotoxin

et al. 2011

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Subtilase cytotoxin (SubAB) is the prototype of a new family of AB 5 cytotoxins produced by Shiga-toxigenic Escherichia coli. Its cytotoxicity is due to its capacity to enter cells and specifically cleave the essential endoplasmic reticulum chaperone BiP. Previous studies have shown that intraperitoneal injection of mice with purified SubAB causes a pathology that overlaps with that seen in human cases of hemolytic-uremic syndrome, as well as dramatic splenic atrophy, suggesting that leukocytes are targeted. Here we investigated SubAB-induced leukocyte changes in the peritoneal cavity, blood, and spleen. After intraperitoneal injection, SubAB bound peritoneal leukocytes (including T and B lymphocytes, neutrophils, and macrophages). SubAB elicited marked leukocytosis, which peaked at 24 h, and increased neutrophil activation in the blood and peritoneal cavity. It also induced a marked redistribution of leukocytes among the three compartments: increases in leukocyte subpopulations in the blood and peritoneal cavity coincided with a significant decline in splenic cells. SubAB treatment also elicited significant increases in the apoptosis rates of CD4 ؉ T cells, B lymphocytes, and macrophages. These findings indicate that apart from direct cytotoxic effects, SubAB interacts with cellular components of both the innate and the adaptive arm of the immune system, with potential consequences for disease pathogenesis.

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Section: Vol 79 2011supporting

confidence: 60%

Section: Vol 79 2011mentioning

confidence: 99%

In Vivo Leukocyte Changes Induced by Escherichia coli Subtilase Cytotoxin

et al. 2011

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“…These neutrophils exhibited enhanced adhesive and cytotoxic properties, and pretreatment of mice with LPS potentiated this effect (127). In vitro, Stx1 increases the number of leukocytes adhering to endothelial cells, an effect that may be enhanced by TNF-␣ (128).…”

Section: Host Responsementioning

confidence: 99%

Pathogenesis of Shiga Toxin-Associated Hemolytic Uremic Syndrome

2001

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“…Purity was analyzed by the supplier, showing only one peak in high-performance liquid chromatography. Stx2 preparation was evaluated for endotoxin contamination by Limulus amebocyte lysate assay as previously described (19) given a contamination less than 40 pg of lipopolysaccharide/g of protein. This Stx2 was tested for toxicity activity on VERO cells, and the 50% cytotoxic dose (CD 50 ) was calculated as previously described (19).…”

Section: Methodsmentioning

confidence: 99%

Development of DNA Vaccines against Hemolytic-Uremic Syndrome in a Murine Model

et al. 2003

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Shiga toxin type 2 (Stx2) produced by Escherichia coli O:157H7 can cause hemolytic-uremic syndrome in children, a disease for which there is neither a vaccine nor an effective treatment. This toxin consists of an enzymatically active A subunit and a pentameric B subunit responsible for the toxin binding to host cells, and also found to be immunogenic in rabbits. In this study we developed eukaryotic plasmids expressing the B subunit gene of Stx2 (pStx2B) and the B subunit plus the gene coding for the A subunit with an active-site deletion (pStx2⌬A). Transfection of eukaryotic cells with these plasmids produced proteins of the expected molecular weight which reacted with specific monoclonal antibodies. Newborn and adult BALB/c mice immunized with two intramuscular injections of each plasmid, either alone or together with the same vector expressing the granulocyte and monocyte colony-stimulating factor (pGM-CSF), elicited a specific Th1-biased humoral response. The effect of pGM-CSF as an adjuvant plasmid was particularly notable in newborn mice and in pStx2B-vaccinated adult mice. Stx2-neutralizing activity, evaluated in vitro on VERO cell monolayers, correlated with in vivo protection. This is the first report using plasmids to induce a neutralizing humoral immune response against the Stx2.

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Shiga Toxin-2 Induces Neutrophilia and Neutrophil Activation in a Murine Model of Hemolytic Uremic Syndrome

Cited by 36 publications

References 44 publications

In Vivo Leukocyte Changes Induced by Escherichia coli Subtilase Cytotoxin

In Vivo Leukocyte Changes Induced by Escherichia coli Subtilase Cytotoxin

Pathogenesis of Shiga Toxin-Associated Hemolytic Uremic Syndrome

Development of DNA Vaccines against Hemolytic-Uremic Syndrome in a Murine Model

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