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Infection and Immunity, April 2000, p. 2374-2378, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Xanthine Oxidase Contributes to Host Defense against Burkholderia cepacia in the p47phoxminus /minus Mouse Model of Chronic Granulomatous Disease

Brahm H. Segal,1,dagger Nobuaki Sakamoto,2,Dagger Mayur Patel,2,§ Kosei Maemura,2,|| Andrew S. Klein,2 Steven M. Holland,1 and Gregory B. Bulkley2,*

Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 and Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 212872

Received 11 June 1999/Returned for modification 27 August 1999/Accepted 13 December 1999

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.

* Corresponding author. Mailing address: Johns Hopkins Hospital, 600 North Wolfe St., Blalock 685, Baltimore, MD 21287. Phone: (410) 955-8500. Fax: (410) 614-3537. E-mail: gbulkley{at}jhmi.edu.

dagger Present address: Department of Infectious Disease, Buffalo General Hospital, Buffalo, NY 14203.

Dagger Present address: Department of Surgery, Tokyo Medical University, Tokyo, Japan.

§ Present address: Vanderbilt University School of Medicine, Nashville, TN 37205.

|| Present address: First Department of Surgery, Kagoshima University School of Medicine, Kagoshima, Japan.

Infection and Immunity, April 2000, p. 2374-2378, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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