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Shiga toxin 2a binds antithrombin and heparin, but does not directly activate platelets
Med Univ Innsbruck, Div Hyg & Med Microbiol, Schopfstr 41, A-6020 Innsbruck, Austria.
Med Univ Innsbruck, Div Hyg & Med Microbiol, Schopfstr 41, A-6020 Innsbruck, Austria.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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2018 (English)In: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 308, no 7, p. 969-976Article in journal (Refereed) Published
Abstract [en]

Escherichia coli-induced hemolytic uremic syndrome (eHUS) is a life-threatening complication of infection with Shiga toxin (Stx), in particular Stx2a-producing Escherichia coli. Enhanced coagulation activation with formation of microthrombi seems to be a key event in development of eHUS. Platelet activation has been postulated as a possible, but controversially debated mechanism. The present study investigated the effect of Stx2a on plasmatic coagulation and platelets. Binding studies were initially performed with ELISA and co-immunoprecipitation and supported by quartz crystal microbalance with dissipation monitoring (QCM-D). Antithrombin (AT) activity was measured using the automated BCS XP (R) system. ROTEM (R) was used for functional coagulation testing. Platelet binding and activation was studied with FACS and light-transmission aggregometry. We found binding of Stx2a to AT, an important inhibitor of blood coagulation, but only a mild albeit significant reduction of AT activity against FXa in the presence of Stx2a. QCM-D analysis also showed binding of Stx2a to heparin and an impaired binding of AT to Stx2a-bound heparin. ROTEM (R) using Stx2a-treated platelet-poor plasma revealed a significant, but only moderate shortening of clotting time. Neither binding nor activation of platelets by Stx2a could be demonstrated. In summary, data of this study suggest that Stx2a binds to AT, but does not induce major effects on plasmatic coagulation. In addition, no interaction with platelets occurred. The well-known non-beneficial administration of heparin in eHUS patients could be explained by the interaction of Stx2a with heparin.

Place, publisher, year, edition, pages
2018. Vol. 308, no 7, p. 969-976
Keywords [en]
Stx2a, Hemolytic uremic syndrome, Plasmatic coagulation, Antithrombin
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-369763DOI: 10.1016/j.ijmm.2018.07.008ISI: 000448628100027PubMedID: 30064820OAI: oai:DiVA.org:uu-369763DiVA, id: diva2:1271535
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2019-12-14Bibliographically approved

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Hamad, Osama A.Fromell, KarinNilsson Ekdahl, KristinaNilsson, Bo

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