Zymosan-induced bacterial translocation: a study of mechanisms.
METHODS
At nonlethal doses, zymosan induces a systemic inflammatory state and promotes bacterial translocation. This study was performed to investigate the mechanisms by which zymosan causes intestinal mucosal injury and bacterial translocation. Bacterial translocation to the mesenteric lymph node was measured 24 hrs after intraperitoneal challenge with saline or zymosan (0.1 mg) in normal (CD-1), congenitally macrophage-hyporesponsive (C3H/HeJ), complement-deficient (DBA/2), or mast cell-deficient (W/Wv) mice. Since zymosan-induced bacterial translocation may be mediated by xanthine oxidase-generated oxidants, bacterial translocation was measured in mice pretreated with the xanthine oxidase inhibitor, allopurinol. To further investigate the role of oxidants in zymosan-induced bacterial translocation, ileal and hepatic levels of xanthine oxidase, myeloperoxidase, conjugated dienes, malondialdehyde, and the antioxidants--superoxide dismutase, catalase, and glutathione peroxidase, were measured.


RESULTS
Zymosan-induced mucosal injury and bacterial translocation occurred to a similar extent (p less than .05) in all four genetic strains of mice, but were reduced in the mice pretreated with allopurinol. Zymosan increased (p less than .03) ileal and hepatic xanthine oxidase activity, while reducing (p less than .01) antioxidant (catalase) activity. There was also evidence of hepatic, but not ileal, lipid peroxidation (conjugated diene) (p less than .05) and neutrophil sequestration (myeloperoxidase) (p less than .01).


CONCLUSIONS
Zymosan-induced intestinal mucosal injury and bacterial translocation do not require complement activation, or the release of macrophage or mast cell products. They appear to be mediated by xanthine oxidase-generated products and associated with disruption of the normal ileal and hepatic oxidant-antioxidant balance.
Deitch
E A
EA
Department of Surgery, Louisiana State University Medical Center, Shreveport 71130-3932.
Specian
R D
RD
Grisham
M B
MB
Berg
R D
RD
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D007082:Ileum / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008198:Lymph Nodes / Q000187:drug effects / Q000382:microbiology; D008297:Male; D008643:Mesentery; D051379:Mice; D008815:Mice, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000187:drug effects; D015054:Zymosan / Q000494:pharmacology*
D000493:Allopurinol; D015054:Zymosan; D014969:Xanthine Oxidase