Endotoxin-induced bacterial translocation: a study of mechanisms.
Previously, we documented that nonlethal doses of endotoxin cause the translocation (escape) of bacteria from the gut to systemic organs. The purpose of this study was to determine which portion(s) of the endotoxin molecule induces bacterial translocation and to examine the role of xanthine oxidase activity in the pathogenesis of endotoxin-induced bacterial translocation. Nonlethal doses of Salmonella endotoxin preparations (wild type, Ra, or Rb), containing the terminal portion of the core polysaccharide, induced bacterial translocation, whereas those preparations lacking the terminal-3 sugars (Rc, Rd, Re, or lipid A) did not induce bacterial translocation. Additionally, only those endotoxin preparations that induced bacterial translocation injured the gut mucosa, increased ileal xanthine dehydrogenase and oxidase activity, and disrupted the normal ecology of the gut flora, resulting in overgrowth with enteric bacilli. Inhibition of xanthine oxidase activity by allopurinol prevented endotoxin (Ra)-induced mucosal injury and reduced the incidence of bacterial translocation from 83% to 30% (p less than 0.01). These results suggest that endotoxin-induced bacterial translocation requires the presence of the terminal core lipopolysaccharide moiety and that xanthine oxidase-generated oxidants are important in the pathogenesis of endotoxin-induced mucosal injury and bacterial translocation.
Department of Surgery, LSU Medical Center, Shreveport 71130-3932.
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D000818:Animals; D018407:Bacterial Physiological Phenomena; D001696:Biomechanical Phenomena; D002432:Cecum / Q000382:microbiology; D002465:Cell Movement / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D007082:Ileum / Q000201:enzymology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012475:Salmonella; D014968:Xanthine Dehydrogenase / Q000378:metabolism
D004731:Endotoxins; D014968:Xanthine Dehydrogenase