Tuberculous Granulomas Are Hypoxic in Guinea Pigs, Rabbits, and Nonhuman Primates

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…

• EM
  Ellison Medical Foundation
• BA
  Bill and Melinda Gates Foundation
• WT
  Wellcome Trust
• NI
  National Institutes of Health
• NI
  National Institute of Allergy and Infectious Diseases