Xanthine oxidase contributes to host defense against Burkholderia cepacia in the p47(phox-/-) mouse model of chronic granulomatous disease

Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH o xidase in which phagocytes are defective in generating superoxide and downs tream microbicidal reactive oxidants, leading to recurrent life-threatening bacterial and fungal infections. Xanthine oxidase (XO) is another enzyme k nown to produce superoxide in many tissues. Using the p47(phox-/-) mouse mo del of CGD, we evaluated the residual antibacterial activity of SO. Clearan ce of Burkholderia cepacia? a major pathogen in CGD, was reduced in p47(pho x-/-) mice compared to that in wild-type mice and was further inhibited in p47(phox-/-) mice by pretreatment with the specific XO inhibitor allopurino l. Hepatic B. cepacia burden aas similar in the two genotypes, but allopuri nol significantly reduced net hepatic killing and killing efficiency only i n p47(phox-/-) mice. Clearance and killing of intravenous Escherichia coli was intact in p47(phox-/-) mice and nas unaffected by pretreatment with all opurinol. Ln CGD, XO mag. contribute to host defense against a subset of re active oxidant-sensitive pathogens.