Circulating xanthine oxidase mediates lung neutrophil sequestration after intestinal ischemia-reperfusion.
Injury to nonpulmonary organ systems often initiates systemic processes that cause recruitment of neutrophils to the lung. We found that rats subjected to intestinal ischemia-reperfusion (I/R) had increased transvascular leak of 125I-labeled albumin into lungs and decreased lung ATP levels (P less than 0.05). In addition, rats subjected to intestinal I/R had increased plasma xanthine oxidase (XO) activity, plasma leukotactic activity for neutrophils, and lung neutrophil retention (assessed by morphometry and myeloperoxidase activity) compared with sham-treated rats (P less than 0.05). By comparison, after intestinal I/R, rats fed an allopurinol- or tungsten-enriched diet had decreased plasma and intestinal XO activities, decreased plasma leukotacic and lung myeloperoxidase (MPO) activities, decreased lung leak, and increased lung ATP levels compared with rats fed control diets (P less than 0.05). Further studies suggested a more specific role for circulating rather than tissue XO in mediating lung neutrophil accumulation but not lung leak. Plasma XO, plasma leukotactic, and lung MPO activities, but not lung leak, increased in rats administered purified XO intravenously. In addition, plasma XO, plasma leukotactic, and lung MPO activities, but not lung leak, decreased in rats administered antisera against XO and then subjected to intestinal I/R. We conclude that circulating XO increases acutely and may contribute to pulmonary retention of neutrophils after an ischemic intestinal insult.
Terada
L S
LS
Webb-Waring Lung Institute, University of Colorado Health Sciences Center, Denver 80262.
Dormish
J J
JJ
Shanley
P F
PF
Leff
J A
JA
Anderson
B O
BO
Repine
J E
JE
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement; D004731:Endotoxins / Q000378:metabolism; D007275:Injections, Intravenous; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014414:Tungsten / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000097:blood* / Q000494:pharmacology / Q000502:physiology
D004731:Endotoxins; D000493:Allopurinol; D009195:Peroxidase; D014969:Xanthine Oxidase; D014414:Tungsten