+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

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

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          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<sup>–9</sup> M SLT-1. Synthesis and release of thromboxane (Tx) A<sub>2</sub>, measured as the stable metabolite TxB<sub>2</sub>, and of 12-(S)-HETE were each increased 1.6 ± 0.1 fold (p < 0.05). No change was observed in the production of PGE<sub>2</sub> or 6-keto-PGF<sub>1α</sub>, the active metabolite of PGI<sub>2</sub>. SLT-1 (10<sup>–9</sup> 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 μ M 12-(S)-HETE. SLT-1 and 0.01 μ M 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.

          Related collections

          Most cited references 3

          • Record: found
          • Abstract: not found
          • Article: not found

          Human renal microvascular endothelial cells as a potential target in the development of the hemolytic uremic syndrome as related to fibrinolysis factor expression, in vitro

            • Record: found
            • Abstract: not found
            • Article: not found

            12-Hydroxyeicosatetraenoic acid reduces prostacyclin production by endothelial cells

              • Record: found
              • Abstract: not found
              • Article: not found

              Adult hemolytic-uremic syndrome. A review of 37 cases

               B. Melnyk (1995)

                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                17 June 1998
                : 21
                : 1
                : 13-21
                Division of Nephrology, Department of Medicine, New York Medical College, Valhalla, N.Y., USA
                25838 Kidney Blood Press Res 1998;21:13–21
                © 1998 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Pages: 9
                Self URI (application/pdf):
                Original Paper


                Comment on this article