Lung injury and complement activation: role of neutrophils and xanthine oxidase.
Evidence is presented that oxygen products generated from xanthine oxidase (XO) may also be involved in the pathogenesis of neutrophil-mediate lung injury following intravascular activation of complement with cobra venom factor (CVF). CVF injection in rats resulted in a rapid increase in plasma of both XO activity (but not xanthine dehydrogenase) and its reaction product, uric acid. These changes were greatly attenuated in allopurinol-treated animals. The appearance of XO activity was paralleled by a rise in plasma of histamine. Prevention of histamine release by pretreatment of rats with cromolyn abolished both the rise in plasma histamine and the increase in XO activity. Since we have previously shown that histamine can enhance XO activity in vitro and in vivo (Am. J. Pathol. 135:203, 1989), these observations suggest that the increase in plasma XO activity following CVF injection is related to the appearance in plasma of histamine. Accordingly, pretreatment of rats with xanthine oxidase inhibitors (allopurinol, lodoxamide) or prevention of histamine release by pretreatment with cromolyn significantly attenuated development of lung injury following injection of CVF. Our data support the concept that oxygen radicals derived from both neutrophils and XO are playing a role in the CVF-induced acute lung injury.
Till
G O
GO
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Friedl
H P
HP
Ward
P A
PA
D000818:Animals; D003167:Complement Activation / Q000187:drug effects; D004546:Elapid Venoms / Q000008:administration & dosage; D005609:Free Radicals; D006632:Histamine / Q000097:blood; D006878:Hydroxides; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000097:blood*
D004546:Elapid Venoms; D005609:Free Radicals; D006878:Hydroxides; C016310:cobra venom factor; D014527:Uric Acid; D006632:Histamine; C031356:hydroxide ion; D014969:Xanthine Oxidase