Xanthine Oxidase Contributes to Host Defense against Burkholderia cepacia in the p47phox−/− Mouse Model of Chronic Granulomatous Disease
AUTOR(ES)
Segal, Brahm H.
FONTE
American Society for Microbiology
RESUMO
Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide and downstream microbicidal reactive oxidants, leading to recurrent life-threatening bacterial and fungal infections. Xanthine oxidase (XO) is another enzyme known to produce superoxide in many tissues. Using the p47phox−/− mouse model of CGD, we evaluated the residual antibacterial activity of XO. Clearance of Burkholderia cepacia, a major pathogen in CGD, was reduced in p47phox−/− mice compared to that in wild-type mice and was further inhibited in p47phox−/− mice by pretreatment with the specific XO inhibitor allopurinol. Hepatic B. cepacia burden was similar in the two genotypes, but allopurinol significantly reduced net hepatic killing and killing efficiency only in p47phox−/− mice. Clearance and killing of intravenous Escherichia coli was intact in p47phox−/− mice and was unaffected by pretreatment with allopurinol. In CGD, XO may contribute to host defense against a subset of reactive oxidant-sensitive pathogens.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=97432Documentos Relacionados
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