title: Clostridium perfringens epsilon-toxin increases permeability of single perfused microvessels of rat mesentery.
abstract: Epsilon-toxin, the primary virulence factor of Clostridium perfringens type D, causes mortality in livestock, particularly sheep and goats, in which it induces an often-fatal enterotoxemia. It is believed to compromise the intestinal barrier and then enter the gut vasculature, from which it is carried systemically, causing widespread vascular endothelial damage and edema. Here we used single perfused venular microvessels in rat mesentery, which enabled direct observation of permeability properties of the in situ vascular wall during exposure to toxin. We determined the hydraulic conductivity (L(p)) of microvessels as a measure of the response to epsilon-toxin. We found that microvessels were highly sensitive to toxin. At 10 microg ml(-1) the L(p) increased irreversibly to more than 15 times the control value by 10 min. At 0.3 microg ml(-1) no increase in L(p) was observed for up to 90 min. The toxin-induced increase in L(p) was consistent with changes in ultrastructure of microvessels exposed to the toxin. Those microvessels exhibited gaps either between or through endothelial cells where perfusate had direct access to the basement membrane. Many endothelial cells appeared necrotic, highly attenuated, and with dense cytoplasm. We showed that epsilon-toxin, in a time- and dose-dependent manner, rapidly and irreversibly compromised the barrier function of venular microvessel endothelium. The results conformed to the hypothesis that epsilon-toxin interacts with vascular endothelial cells and increases the vessel wall permeability by direct damage of the endothelium.
authors.affiliation: Department of Physiology and Membrane Biology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA. rhadamson@ucdavis.edu
authors.forename: R H
authors.initials: RH
authors.lastname: Adamson
authors.forename: J C
authors.initials: JC
authors.lastname: Ly
authors.forename: M
authors.initials: M
authors.lastname: Fernandez-Miyakawa
authors.forename: S
authors.initials: S
authors.lastname: Ochi
authors.forename: J
authors.initials: J
authors.lastname: Sakurai
authors.forename: F
authors.initials: F
authors.lastname: Uzal
authors.forename: F E
authors.initials: FE
authors.lastname: Curry
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins / Q000276:immunology / Q000494:pharmacology*; D003016:Clostridium perfringens; D008642:Mesenteric Veins / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D010539:Permeability / Q000187:drug effects; D051381:Rats; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; C039811:Clostridium perfringens epsilon-toxin