For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
37
views
27
references
 Top references
cited by
0
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      855
      similar
       All similar

      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

      Submit here before July 31, 2024

      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Effect of Shiga Toxin on Weibel-Palade Bodies in Primary Human Endothelial Cells

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          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.

          Abstract

          Background/Aims

          Diarrhea-associated hemolytic uremic syndrome is associated with the presence of Shiga toxin (Stx1, Stx2 and several variants) in the circulation. The aim of this study is to examine the possible triggering effect of Stx1 on the exocytosis of Weibel-Palade bodies (WPbs).

          Methods

          Cultured human umbilical venous endothelial cells (HUVECs) and glomerular microvascular endothelial cells (GMVECs) were stimulated by thrombin and Stx1 in both static and flowing conditions. The amount of secreted von Willebrand factor (VWF) in the supernatant as well as the remaining intracellular fraction was determined.

          Results

          In HUVECs and in 2 out of 4 GMVECs, the stimulation of Stx1 in flow at 1 dyne/cm 2 resulted in a decrease of intracellular VWF. This is contrary to the results of Stx1 applied in static conditions. At a higher flow rate of 5 dyne/cm 2, no effect in GMVECs was observed.

          Conclusion

          Stx1 can contribute, via an effect on WPbs, to the exocytosis of WPbs in flow conditions in HUVECs and probably in GMVECs. This results in the release of VWF, suggesting an initiating role of the coagulation system in the pathogenesis.

          Related collections

          Most cited references27

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

          Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome.

          Phillip Tarr, Carrie A Gordon, Wayne Chandler (2005)
          Most cases of diarrhoea-associated haemolytic uraemic syndrome (HUS) are caused by Shiga-toxin-producing bacteria; the pathophysiology differs from that of thrombotic thrombocytopenic purpura. Among Shiga-toxin-producing Escherichia coli (STEC), O157:H7 has the strongest association worldwide with HUS. Many different vehicles, in addition to the commonly suspected ground (minced) beef, can transmit this pathogen to people. Antibiotics, antimotility agents, narcotics, and non-steroidal anti-inflammatory drugs should not be given to acutely infected patients, and we advise hospital admission and administration of intravenous fluids. Management of HUS remains supportive; there are no specific therapies to ameliorate the course. The vascular injury leading to HUS is likely to be well under way by the time infected patients seek medical attention for diarrhoea. The best way to prevent HUS is to prevent primary infection with Shiga-toxin-producing bacteria.
          Article 0 comments Cited 390 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Dynamics and plasticity of Weibel-Palade bodies in endothelial cells.

            Jan Voorberg, Mariska G Rondaij, Astrid Kragt … (2006)
            Agonist-induced release of endothelial cell specific storage granules, designated Weibel-Palade bodies (WPBs), provides the endothelium with the ability to rapidly respond to changes in its micro-environment. Originally being defined as an intracellular storage pool for von Willebrand factor (VWF), it has recently been shown that an increasing number of other components, including P-selectin, interleukin (IL)-8, eotaxin-3, endothelin-1, and angiopoietin-2, is present within this subcellular organelle, implicating a role for WPB exocytosis in inflammation, hemostasis, regulation of vascular tone and angiogenesis. Recent studies emphasize that WPBs provide a dynamic storage compartment whose contents can be regulated depending on the presence of inflammatory mediators in the vascular micro-environment. Additionally, release of WPBs is tightly regulated and feedback mechanisms have been identified that prevent excessive release of bioactive components from this subcellular organelle. The ability to regulate both contents and exocytosis of WPBs endows these endothelial cell specific organelles with a remarkable plasticity. This is most likely needed to allow for controlled delivery of bioactive components into the circulation on vascular perturbation.
            Article 0 comments Cited 78 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Thrombin generates previously unidentified C5 products that support the terminal complement activation pathway.

              J Krisinger, Timothy Myles, Verena Goebeler … (2012)
              The coagulation and complement pathways simultaneously promote homeostasis in response to injury but cause tissue damage when unregulated. Mechanisms by which they cooperate are poorly understood. To delineate their interactions, we studied the effects of thrombin and C5 convertase on C5 in purified and plasma-based systems, measuring release of the anaphylatoxin C5a, and generation of C5b, the initial component of the lytic membrane attack complex. Thrombin cleaved C5 poorly at R751, yielding minimal C5a and C5b. However, thrombin efficiently cleaved C5 at a newly identified, highly conserved R947 site, generating previously undescribed intermediates C5(T) and C5b(T). Tissue factor-induced clotting of plasma led to proteolysis of C5 at a thrombin-sensitive site corresponding to R947 and not R751. Combined treatment of C5 with thrombin and C5 convertase yielded C5a and C5b(T), the latter forming a C5b(T)-9 membrane attack complex with significantly more lytic activity than with C5b-9. Our findings provide a new paradigm for complement activation, in which thrombin and C5 convertase are invariant partners, enhancing the terminal pathway via the generation of newly uncovered C5 intermediates. Delineating the molecular links between coagulation and complement will provide new therapeutic targets for diseases associated with excess fibrin deposition and complement activation.
              Article 0 comments Cited 71 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Nephron Extra
                Journal ID (iso-abbrev): Nephron Extra
                Journal ID (publisher-id): NNE
                Title: Nephron Extra
                Publisher: S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch )
                ISSN (Print): 1664-5529
                ISSN (Electronic): 1664-5529
                Publication date Collection: Jan-Apr 2014
                Publication date (Electronic): 8 July 2014
                Publication date PMC-release: 8 July 2014
                Volume: 4
                Issue: 2
                Pages: 101-107
                Affiliations
                [1] aDepartment of Paediatric Nephrology, The Netherlands
                [2] bCentral Hematology Laboratory, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
                [3] cDepartment of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands
                [4] dDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands
                Author notes
                *Joyce Geelen, Bornsestraat 15, NL-7595 LH Weerselo (The Netherlands), E-Mail joycegeelen@ 123456gmail.com
                Article
                Publisher ID: nne-0004-0101
                DOI: 10.1159/000363299
                PMC ID: 4130816
                SO-VID: a1cc3978-d7fb-4da5-a253-464252734871
                Copyright © Copyright © 2014 by S. Karger AG, Basel
                License:

                This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Users may download, print and share this work on the Internet for noncommercial purposes only, provided the original work is properly cited, and a link to the original work on http://www.karger.com and the terms of this license are included in any shared versions.

                History
                Page count
                Figures: 4, Tables: 1, References: 24, Pages: 7
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Nephrology
                Keywords: shiga toxin,weibel-palade bodies,von willebrand factor,endothelial cells
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: shiga toxin, weibel-palade bodies, von willebrand factor, endothelial cells

                Comments

                Comment on this article