Mediator-induced activation of xanthine oxidase in endothelial cells.
Rat pulmonary artery endothelial cells incubated with human serum that has been complement-activated by addition of cobra venom factor reveal a pronounced conversion of xanthine dehydrogenase to xanthine oxidase. This process requires the availability of the fifth component of complement (C5) but not the presence of other components (C2 and C6-C9). The phenomenon can be reproduced by addition to endothelial cells of purified human recombinant C5a but not C5a desArg or C3a. The enzyme conversion process is relatively rapid (occurring within 5-10 min), requires the presence of intact endothelial cells, and does not require protein synthesis. Similar effects on endothelial cells have been obtained with human recombinant tumor necrosis factor alpha and the chemotactic peptide N-formyl-Met-Leu-Phe. In contrast, bradykinin, recombinant human interleukin 1 beta, and phorbol ester lack this biological activity. These findings suggest novel effects of inflammatory mediators on endothelial cells.
Friedl
H P
HP
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Till
G O
GO
Ryan
U S
US
Ward
P A
PA
D000818:Animals; D001769:Blood; D003167:Complement Activation; D003182:Complement C5 / Q000502:physiology*; D015936:Complement C5a / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology; D004546:Elapid Venoms / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000201:enzymology*; D004789:Enzyme Activation; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000201:enzymology; D051381:Rats; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*
D003182:Complement C5; D004546:Elapid Venoms; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C016310:cobra venom factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D003165:Complement System Proteins; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase