Endotoxin-induced bacterial translocation and mucosal permeability: role of xanthine oxidase, complement activation, and macrophage products.
METHODS
Previously, we documented that nonlethal doses of endotoxin injure the intestinal mucosal barrier and promote bacterial translocation from the gut to systemic organs. The current study was performed to determine the role of cytokines and complement activation in the pathogenesis of endotoxin-induced mucosal injury and bacterial translocation, as well as to quantify the magnitude of endotoxin-induced intestinal mucosal permeability.


RESULTS
The frequency of endotoxin-induced bacterial translocation was similar between normal outbred (88%), complement deficient (67%), and macrophage-hyporesponsive (55%) mice, indicating that neither complement nor macrophage activation is necessary for endotoxin-induced bacterial translocation to occur. As early as 2 hrs after endotoxin challenge, there was evidence of a greater than two-fold increase in ileal (p = .008) but not jejunal (p = .11) permeability as measured by the clearance of 51Cr EDTA. Both the increase in endotoxin-induced ileal permeability and the occurrence of bacterial translocation were largely prevented by pretreatment with allopurinol, a competitive inhibitor of xanthine oxidase.


CONCLUSIONS
These results suggest that endotoxin-induced bacterial translocation, mucosal injury, and ileal permeability are mediated via activation of xanthine oxidase, and not through complement activation or the liberation of macrophage products.
Deitch
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Department of Surgery, Louisiana State University Medical Center, Shreveport 71130-3932.
Specian
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Berg
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D000818:Animals; D002464:Cell Migration Inhibition; D003167:Complement Activation / Q000502:physiology*; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000502:physiology*; D004926:Escherichia coli / Q000302:isolation & purification; D007082:Ileum / Q000378:metabolism / Q000382:microbiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism*; D008643:Mesentery / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D014969:Xanthine Oxidase / Q000502:physiology*
D004731:Endotoxins; D014969:Xanthine Oxidase