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Title:Pathogenesis of Fumonisin Toxicosis in Swine
Author(s):Gumprecht, Laura Anne
Doctoral Committee Chair(s):Wanda Haschek-Hock
Department / Program:Veterinary Clinical Medicine
Discipline:Veterinary Clinical Medicine
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Biology, Veterinary Science
Abstract:Fumonisins are a recently identified group of mycotoxins that are worldwide contaminants of corn produced by Fusarium moniliforme. They induce species-specific disease, including leukoencephalomalacia in horses and pulmonary edema in pigs, but little is known about the pathogenesis of disease. Fumonisins inhibit ceramide synthase in the sphingolipid biosynthetic pathway, but the subsequent elevation of tissue sphingoid bases is not always associated with disease. The goal of these studies was to elucidate the pathogenesis of fumonisin toxicoses in swine. To study the pathogenesis of pulmonary edema, we examined the early events in the development of fumonisin-induced hepatotoxicity and pulmonary edema in pigs. Pigs were fed fumonisin-contaminated culture material at 20 mg fumonisin B1/kg body weight/day, and were euthanized on 0, 1, 2, 3, 4, or 5 days after initial exposure to fumonisin, or when pulmonary edema developed. Elevations in sphingoid bases began in tissues of fumonisin-treated pigs (day 1) before the development of hepatotoxicity (day 2) or pulmonary edema (days 3 and 4), indicating sphingolipids could play a role in the development of acute toxicosis in swine. Ultrastructurally, alveolar endothelial cells contained unique perinuclear accumulations of membranous material beginning on day 2. These were specific to porcine alveolar capillary endothelium, since endothelia from other target and non-target tissues of fumonisin-treated pigs, sheep, rabbits, and rats did not have such lesions. These ultrastructural changes could not be induced in vitro using cultures of porcine pulmonary artery endothelial cells. Based on previous findings of decreased pulmonary clearance of intravenous bacteria in fumonisin-treated pigs, we hypothesized that fumonisins may be immunosuppressive. At low doses (2 mg/kg body weight), fumonisins elevated sphingoid bases in immune tissues and cells, but did not adversely affect the response to pseudorabies vaccination either humorally (antibody titers) or by cell-mediated means (lymphocyte blastogenic response). Non-specific immunity, specifically macrophage phagocytosis, was inhibited in both RAW cells exposed in vitro to fumonisin B1 at >25 muM, and alveolar macrophages isolated from fumonisin-treated pigs (15 mg/kg body weight for 3 days). Sphingoid bases were elevated in both cell types. Inhibition of phagocytosis may increase susceptibility of pigs to bacterial infection.
Issue Date:1998
Type:Text
Language:English
Description:176 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1998.
URI:http://hdl.handle.net/2142/87138
Other Identifier(s):(MiAaPQ)AAI9912249
Date Available in IDEALS:2015-09-28
Date Deposited:1998


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