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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates
Infection and Immunity, Volume 76, No. 6, Year 2008
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Description
Understanding the physical characteristics of the local microenvironment in which Mycobacterium tuberculosis resides is an important goal that may allow the targeting of metabolic processes to shorten drug regimens. Pimonidazole hydrochloride (Hypoxyprobe) is an imaging agent that is bioreductively activated only under hypoxic conditions in mammalian tissue. We employed this probe to evaluate the oxygen tension in tuberculous granulomas in four animal models of disease: mouse, guinea pig, rabbit, and nonhuman primate. Following infusion of pimonidazole into animals with established infections, lung tissues from the guinea pig, rabbit, and nonhuman primate showed discrete areas of pimonidazole adduct formation surrounding necrotic and caseous regions of pulmonary granulomas by immunohistochemical staining. This labeling could be substantially reduced by housing the animal under an atmosphere of 95% O2. Direct measurement of tissue oxygen partial pressure by surgical insertion of a fiber optic oxygen probe into granulomas in the lungs of living infected rabbits demonstrated that even small (3-mm) pulmonary lesions were severely hypoxic (1.6 ± 0.7 mm Hg). Finally, metronidazole, which has potent bactericidal activity in vitro only under low-oxygen culture conditions, was highly effective at reducing total-lung bacterial burdens in infected rabbits. Thus, three independent lines of evidence support the hypothesis that hypoxic microenvironments are an important feature of some lesions in these animal models of tuberculosis. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Via, L. E.
United States, Bethesda
National Institutes of Health Nih
Lin, Philana Ling
United States, Pittsburgh
University of Pittsburgh School of Medicine
Klein, Edwin C.
United States, Pittsburgh
University of Pittsburgh School of Medicine
Manjunatha, Ujjini H.
United States, Bethesda
National Institutes of Health Nih
Gonzales, Jacqueline
United States, Bethesda
National Institutes of Health Nih
Park, Seungkyu
South Korea, Seoul
Minster for Health, Welfare and Family Affairs, Korea
Cho, Sangnae Ray
South Korea, Seoul
Yonsei University College of Medicine
McMurray, David Neil
United States, Bryan
Texas A&m University Health Science Center
Flynn, Jo Anne L.
United States, Pittsburgh
University of Pittsburgh School of Medicine
Barry, Clifton Earl
United States, Bethesda
National Institutes of Health Nih
Statistics
Citations: 515
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1128/IAI.01515-07
ISSN:
00199567
Research Areas
Health System And Policy
Noncommunicable Diseases
Study Locations
Guinea