Effect of TNF-α, shiga toxin and calcium ionophore on weibel-palade body content of endothelial cells: Possible implications for the hemolytic uremic syndrome

1995 ◽  
Vol 79 (4) ◽  
pp. 415-421 ◽  
Author(s):  
Susan A. Kaye ◽  
Tom G. Obrig
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Calcium Ionophore ◽  
Tnf Α ◽  
Uremic Syndrome

scholarly journals Absence of interleukin-10 reduces progression of shiga toxin-induced hemolytic uremic syndrome

2021 ◽  
Vol 135 (3) ◽  
pp. 575-588
Author(s):  
Gonzalo Ezequiel Pineda ◽  
Bárbara Rearte ◽  
María Florencia Todero ◽  
Andrea Cecilia Bruballa ◽  
Alan Mauro Bernal ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Renal Damage ◽  
Polymorphonuclear Neutrophils ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasma Urea ◽  
Tnf Α ◽  
Uremic Syndrome ◽  
Anti Inflammatory

Abstract Hemolytic Uremic Syndrome (HUS), a disease triggered by Shiga toxin (Stx), is characterized by hemolytic anemia, thrombocytopenia and renal failure. The inflammatory response mediated by polymorphonuclear neutrophils (PMNs) and monocytes is essential to HUS onset. Still, the role of anti-inflammatory cytokines is less clear. The deficiency of IL-10, an anti-inflammatory cytokine, leads to severe pathology in bacterial infections but also to beneficial effects in models of sterile injury. The aim of this work was to analyze the role of IL-10 during HUS. Control and IL-10 lacking mice (IL-10−/−) were intravenously injected with Stx type 2 (Stx2) and survival rate was evaluated. PMN and circulating and renal pro- and anti-inflammatory factors were analyzed by FACS and enzyme-linked immunosorbent assay (ELISA) respectively. IL-10−/− mice showed a higher survival associated with lower renal damage reflected by reduced plasma urea and creatinine levels than control mice. Circulating PMN increased at 72 h in both mouse strains accompanied by an up-regulation of CD11b in control mice. In parallel, renal PMN were significantly increased only in control mice after toxin. Plasma TNF-α, IL-6 and corticosterone levels were higher increased in IL-10−/− than control mice. Simultaneously renal TNF-α raised constantly but was accompanied by increased TGF-β levels in IL-10−/− mice. These results demonstrate that the profile of circulating and renal cytokines after Stx2 differed between strains suggesting that balance of these factors could participate in renal protection. We conclude that IL-10 absence has a protective role in an experimental model of HUS by reducing PMN recruitment into kidney and renal damage, and increasing mice survival.

Binding of [125I]Shiga-like Toxin-1 to Human Endothelial Cells: Implications for the Pathogenesis of Shiga Toxin-associated Hemolytic Uremic Syndrome

Endothelium ◽  
1995 ◽  
Vol 3 (2) ◽  
pp. 159-170 ◽  
Author(s):  
Chandra B. Louise ◽  
Timothy P. Moran ◽  
Clifford A. Lingwood ◽  
Peter J. Del Vecchio ◽  
David J. Culp ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Human Endothelial Cells ◽  
Uremic Syndrome

scholarly journals Complement Activation Contributes to the Pathophysiology of Shiga Toxin-Associated Hemolytic Uremic Syndrome

2019 ◽  
Vol 7 (1) ◽  
pp. 15 ◽  
Author(s):  
Simona Buelli ◽  
Carlamaria Zoja ◽  
Giuseppe Remuzzi ◽  
Marina Morigi
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Complement Activation ◽  
Close Contact ◽  
Thrombus Formation ◽  
Microvascular Dysfunction ◽  
Experimental Models ◽  
Filtration Barrier ◽  
Uremic Syndrome

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections have become a threat to public health globally because of the severe illnesses that they can trigger, such as hemorrhagic colitis and the post-diarrheal hemolytic uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. Glomerular endothelial cells are primary targets of Stx which, after binding to its specific receptor globotriaosylceramide, upregulates proinflammatory proteins involved both in the recruitment and adhesion of leukocytes and thrombus formation at the site of endothelial injury. In this review, we discuss the role of complement activation in promoting glomerular microvascular dysfunction, providing evidence from experimental models and patients with STEC-HUS. Within the glomerulus, an important target for Stx-induced complement activation is the podocyte, a cell type that is in close contact with endothelial cells and participates in maintaining the filtration barrier. Recently, podocyte injury and loss have been indicated as potential risk factors for long-term renal sequelae in patients with STEC-HUS. Therapeutic approaches targeting the complement system, that may be useful options for patients with STEC-HUS, will also be discussed.

Tissue-resident macrophages mediate neutrophil recruitment and kidney injury in shiga toxin-induced hemolytic uremic syndrome.

2021 ◽  
Author(s):  
Julia K. Lill ◽  
Stephanie Thiebes ◽  
Judith-Mira Pohl ◽  
Jenny Bottek ◽  
Nirojah Subramaniam ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Kidney Injury ◽  
Neutrophil Recruitment ◽  
Uremic Syndrome

scholarly journals Hemoconcentration and predictors in Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS)

2021 ◽  
Author(s):  
Sebastian Loos ◽  
Jun Oh ◽  
Laura van de Loo ◽  
Markus J. Kemper ◽  
Martin Blohm ◽  
...  
Keyword(s):  
Risk Factor ◽  
Serum Creatinine ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Neurological Symptoms ◽  
Fluid Loss ◽  
Good Prediction ◽  
E Coli ◽  
Complicated Course ◽  
Uremic Syndrome

Abstract Background Hemoconcentration has been identified as a risk factor for a complicated course in Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS). This single-center study assesses hemoconcentration and predictors at presentation in STEC-HUS treated from 2009–2017. Methods Data of 107 pediatric patients with STEC-HUS were analyzed retrospectively. Patients with mild HUS (mHUS, definition: max. serum creatinine < 1.5 mg/dL and no major neurological symptoms) were compared to patients with severe HUS (sHUS, definition: max. serum creatinine ≥ 1.5 mg/dL ± major neurological symptoms). Additionally, predictors of complicated HUS (dialysis ± major neurological symptoms) were analyzed. Results Sixteen of one hundred seven (15%) patients had mHUS. Admission of patients with sHUS occurred median 2 days earlier after the onset of symptoms than in patients with mHUS. On admission, patients with subsequent sHUS had significantly higher median hemoglobin (9.5 g/dL (3.6–15.7) vs. 8.5 g/dL (4.2–11.5), p = 0.016) than patients with mHUS. The product of hemoglobin (g/dL) and LDH (U/L) (cutoff value 13,302, sensitivity 78.0%, specificity of 87.5%) was a predictor of severe vs. mild HUS. Creatinine (AUC 0.86, 95% CI 0.79–0.93) and the previously published score hemoglobin (g/dL) + 2 × creatinine (mg/dL) showed a good prediction for development of complicated HUS (AUC 0.87, 95% CI 0.80–0.93). Conclusions At presentation, patients with subsequent severe STEC-HUS had a higher degree of hemoconcentration. This underlines that fluid loss or reduced fluid intake/administration may be a risk factor for severe HUS. The good predictive value of the score hemoglobin (g/dL) + 2 × creatinine (mg/dL) for complicated HUS could be validated in our cohort. Graphical abstract

scholarly journals Whole-genome characterization of hemolytic uremic syndrome-causing Shiga toxin-producing Escherichia coli in Sweden

Virulence ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1296-1305
Author(s):  
Ying Hua ◽  
Milan Chromek ◽  
Anne Frykman ◽  
Cecilia Jernberg ◽  
Valya Georgieva ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Whole Genome ◽  
Genome Characterization ◽  
Uremic Syndrome
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