Purified verotoxins of Escherichia coli O157:H7 decrease prostacyclin synthesis by endothelial cells

Karch, Helge; Bitzan, Martin; Pietsch, R; Stenger, K; Wulffen, H. von; Heesemann, Jürgen; Düsing, Rainer

doi:10.1016/0882-4010(88)90024-1

Cited by 48 publications

(23 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Decreased production of prostacyclin (PGI 2 ), a potent inhibitor of platelet aggregation produced in endothelium, has been demonstrated in several studies of HUS patients [9]. Decreased production of PGI 2 has also been demonstrated in rat aortic segments following exposure to SLT-1 and 2 [21]. Synthesis of TxA 2 , a platelet-aggregating prostanoid, has been reported to be increased in childhood HUS [20].…”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Glomerular Endothelial Cell Injury Mediated by Shiga-Like Toxin-1

Adler

Bollu²

1998

Kidney Blood Press Res

View full text Add to dashboard Cite

The hemolytic uremic syndrome is an important cause of acute renal failure and is often associated with prior infection with enterotoxigenic strains of Escherichia coli. Significant pathologic changes in the glomerulus include endothelial cell swelling, detachment, and intravascular coagulation. We investigated the potential pathogenetic mechanisms of this disease by exposing cultured rat glomerular endothelial cells to shiga-like toxin 1 (SLT-1). Glomerular endothelial cell viability and protein synthesis were not affected by 10^–9 M SLT-1. Synthesis and release of thromboxane (Tx) A₂, measured as the stable metabolite TxB₂, and of 12-(S)-HETE were each increased 1.6 ± 0.1 fold (p < 0.05). No change was observed in the production of PGE₂ or 6-keto-PGF_1α, the active metabolite of PGI₂. SLT-1 (10^–9 M) significantly increased cell retraction and the formation of gaps in the glomerular endothelial cell monolayer for up to 6 h following exposure. A similar effect was seen with 0.1 μM 12-(S)-HETE. SLT-1 and 0.01 μM 12-(S)-HETE also significantly decreased adhesion of glomerular endothelial cells to fibronectin (75 ± 4 and 65 ± 2% of control, respectively; p < 0.001) and laminin (81 ± 5 and 67 ± 4% of control, respectively; p < 0.01). These results support a role for SLT-1 in the production of the pathologic changes seen in the hemolytic uremic syndrome through stimulation of production of procoagulant, vasoconstrictor arachidonic acid metabolites with potential to produce endothelial injury and through alterations in glomerular endothelial cell adhesion to components of the glomerular basement membrane.

show abstract

Section: Discussionmentioning

confidence: 93%

“…Abnormalities of arachidonic acid metabolites in HUS have been described, including decreased production of PGI 2 and increased production of Tx [9,19,20]. In vitro, SLT-1 and SLT-2 inhibit release of PGI 2 from large vessel endothelium [21].…”

Section: Introductionmentioning

confidence: 99%

Glomerular Endothelial Cell Injury Mediated by Shiga-Like Toxin-1

Adler

Bollu²

1998

Kidney Blood Press Res

View full text Add to dashboard Cite

show abstract

“…Considering that dialysis often used to treat the renal failure associated with HUS is ineffective in removing the 70kD verocytotoxin [10], TPE may reduce the significant morbidity and mortality of E. coli O157:H7 HUS.…”

Section: Discussionmentioning

confidence: 99%

Consanguineous hemolytic uremic syndrome secondary to Escherichia coli O157:H7 infection treated with aggressive therapeutic plasma exchange

Downes

Allen

Sarode

et al. 2001

J of Clinical Apheresis

View full text Add to dashboard Cite

We describe the successful management of an elderly husband and wife with Escherichia coli O157:H7 associated hemolytic uremic syndrome (HUS) treated with aggressive therapeutic plasma exchange (TPE) with replacement with fresh frozen plasma. Following twelve TPEs (three 1.5 volume; nine 1 volume), the husband's platelet count increased from 45 x 10(9)/L to 183 x 10(9)/L. Following ten 1.5 volume TPEs, the wife's platelet count increased from 30 x 10(9)/L to 193 x 10(9)/L. This is the first known occurrence of E. coli O157:H7 associated HUS in an elderly husband and wife successfully treated with aggressive TPE. We conclude that early, aggressive TPE should be considered and may be life-saving for E coli O157:H7 associated HUS in the elderly.

show abstract

“…31-33]. It is suggested that a direct toxic effect of verocytotoxin (a shiga-like toxin) on microvascular endothelium results in inhibition of prosta cyclin, a potent endothelial-derived inhibitor of platelet aggregation, providing the initial insult leading to the development of TMA [20,32], Whether the altered im mune system in HIV infection facilitates verocytotoxininduced endothelial injury remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Disparate Prognosis of Thrombotic Microangiopathy in HIV-Infected Patients with and without AIDS

et al. 1996

View full text Add to dashboard Cite

Thrombotic microangiopathy (TMA) is more common in HIV-infected individuals than in the normal population. In idiopathic TMA, plasmapheresis with or without prednisone decreases the mortality rate from almost 100 to 10%. Patients with HIV-associated TMA, who do not have AIDS, have a similar favorable outcome when treated with plasmapheresis. However, all 12 patients previously reported with AIDS-associated TMA have died. We report another patient with AIDS-associated TMA, who had a fulminant hospital course and died despite plasmapheresis. None of the reported AIDS-associated TMA patients had evidence of opportunistic infections, sepsis or disseminated malignancies at the time of their death. Since many infections and malignancies can be associated with TMA, it is possible that TMA can be an association of the terminal illness rather than an independent cause of death in AIDS patients. To examine this possibility, we reviewed the charts of all the patients who were hospitalized and died of AIDS at our medical centers from 1987 to 1994. Of the 214 patients reviewed, 15 patients (7%) had evidence of TMA at the time of their death. Seven of the 15 patients (47%) had no direct cause of death other than TMA. The remaining 8 patients had evidence of sepsis and other overwhelming infections. In conclusion, TMA is common in AIDS patients. While HIV-associated TMA has a good prognosis similar to that of idiopathic TMA, AIDS-associated TMA has a grave prognosis. The etiology of the higher mortality in AIDS-associated TMA as compared to HIV-associated TMA remains unclear.

show abstract

Purified verotoxins of Escherichia coli O157:H7 decrease prostacyclin synthesis by endothelial cells

Cited by 48 publications

References 25 publications

Glomerular Endothelial Cell Injury Mediated by Shiga-Like Toxin-1

Glomerular Endothelial Cell Injury Mediated by Shiga-Like Toxin-1

Consanguineous hemolytic uremic syndrome secondary to Escherichia coli O157:H7 infection treated with aggressive therapeutic plasma exchange

Disparate Prognosis of Thrombotic Microangiopathy in HIV-Infected Patients with and without AIDS

Contact Info

Product

Resources

About