title: Shiga toxin of enterohaemorrhagic Escherichia coli directly injures developing human erythrocytes.
abstract: Haemolytic anaemia is one of the characteristics of life-threatening extraintestinal complications in humans during infection with enterohaemorrhagic Escherichia coli (EHEC). Shiga toxins (Stxs) of EHEC preferentially damage microvascular endothelial cells of the kidney and the brain, whereby occluded small blood vessels may elicit anaemia through mechanical erythrocyte disruption. Here we show for the first time that Stx2a, the major virulence factor of EHEC, is also capable of direct targeting developing human erythrocytes. We employed an ex vivo erythropoiesis model using mobilized CD34(+) haematopoietic stem/progenitor cells from human blood and monitored expression of Stx receptors and Stx2a-mediated cellular injury of developing erythrocytes. CD34(+) haematopoietic stem/progenitor cells were negative for Stx2a receptors and resistant towards the toxin. Expression of Stx2a-binding glycosphingolipids and toxin sensitivity was apparent immediately after initiation of erythropoietic differentiation, peaked for basophilic and polychromatic erythroblast stages and declined during maturation into orthochromatic erythroblasts and reticulocytes, which became highly refractory to Stx2a. The observed Stx-mediated toxicity towards erythroblasts during the course of erythropoiesis might contribute, although speculative at this stage of research, to the anaemia caused by Stx-producing pathogens.
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany.
authors.forename: Josefine
authors.initials: J
authors.lastname: Betz
authors.affiliation: Pediatric Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Dorn
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany.|Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany.
authors.forename: Ivan U
authors.initials: IU
authors.lastname: Kouzel
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauwens
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany.|Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Meisen
authors.affiliation: Center for Biomedical Optics, University of Münster, Münster, Germany.|Biomedical Technology Center, University of Münster, Münster, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Kemper
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Bielaszewska
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Mormann
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Weymann
authors.affiliation: Institute of Transfusion Medicine and Transplantation Immunology, University of Münster, Münster, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Sibrowski
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Karch
authors.affiliation: Institute of Transfusion Medicine and Transplantation Immunology, University of Münster, Münster, Germany.|Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Schlenke
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany. jm@uni-muenster.de.|Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany. jm@uni-muenster.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Müthing
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D054324:Enterohemorrhagic Escherichia coli / Q000502:physiology*; D004912:Erythrocytes / Q000382:microbiology / Q000502:physiology; D006410:Hematopoiesis / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000382:microbiology / Q000502:physiology*; D006801:Humans; D022621:Shiga Toxin / Q000494:pharmacology*
chemical_list: D022621:Shiga Toxin