title: Rapid cytopathic effects of Clostridium perfringens beta-toxin on porcine endothelial cells.
abstract: Clostridium perfringens type C isolates cause fatal, segmental necro-hemorrhagic enteritis in animals and humans. Typically, acute intestinal lesions result from extensive mucosal necrosis and hemorrhage in the proximal jejunum. These lesions are frequently accompanied by microvascular thrombosis in affected intestinal segments. In previous studies we demonstrated that there is endothelial localization of C. perfringens type C beta-toxin (CPB) in acute lesions of necrotizing enteritis. This led us to hypothesize that CPB contributes to vascular necrosis by directly damaging endothelial cells. By performing additional immunohistochemical studies using spontaneously diseased piglets, we confirmed that CPB binds to the endothelial lining of vessels showing early signs of thrombosis. To investigate whether CPB can disrupt the endothelium, we exposed primary porcine aortic endothelial cells to C. perfringens type C culture supernatants and recombinant CPB. Both treatments rapidly induced disruption of the actin cytoskeleton, cell border retraction, and cell shrinkage, leading to destruction of the endothelial monolayer in vitro. These effects were followed by cell death. Cytopathic and cytotoxic effects were inhibited by neutralization of CPB. Taken together, our results suggest that CPB-induced disruption of endothelial cells may contribute to the pathogenesis of C. perfringens type C enteritis.
authors.affiliation: Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Gurtner
authors.forename: Francesca
authors.initials: F
authors.lastname: Popescu
authors.forename: Marianne
authors.initials: M
authors.lastname: Wyder
authors.forename: Esther
authors.initials: E
authors.lastname: Sutter
authors.forename: Friederike
authors.initials: F
authors.lastname: Zeeh
authors.forename: Joachim
authors.initials: J
authors.lastname: Frey
authors.forename: Conrad
authors.initials: C
authors.lastname: von Schubert
authors.forename: Horst
authors.initials: H
authors.lastname: Posthaus
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003015:Clostridium Infections / Q000382:microbiology / Q000473:pathology; D003016:Clostridium perfringens / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D003106:Colon / Q000473:pathology; D042783:Endothelial Cells / Q000382:microbiology* / Q000473:pathology; D004751:Enteritis / Q000382:microbiology / Q000473:pathology / Q000662:veterinary; D009500:Neutralization Tests; D011994:Recombinant Proteins; D013270:Stomach / Q000473:pathology; D013552:Swine
chemical_list: D001427:Bacterial Toxins; C031884:CPB protein, Clostridium perfringens; D011994:Recombinant Proteins
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