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Infection and Immunity, April 2000, p. 2374-2378, Vol. 68, No. 4
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
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
p47phox
/
Mouse Model of Chronic
Granulomatous Disease



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