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Role For Inducible Nitric Oxide Synthase In Protection From Chronic Chlamydia Trachomatis Urogenital Disease In Mice And Its Regulation By Oxygen Free Radicals
K. Ramsey, I. Sigar, S. Rana, J. Gupta, S. Holland, G. Byrne
Published 2001 · Biology, Medicine
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ABSTRACT It has been previously reported that although inducible nitric oxide synthase (iNOS) gene knockout (NOS2−/−) mice resolve Chlamydia trachomatis genital infection, the production of reactive nitrogen species (RNS) via iNOS protects a significant proportion of mice from hydrosalpinx formation and infertility. We now report that higher in vivo RNS production correlates with mouse strain-related innate resistance to hydrosalpinx formation. We also show that mice with a deletion of a key component of phagocyte NADPH oxidase (p47phox−/−) resolve infection, produce greater amounts of RNS in vivo, and sustain lower rates of hydrosalpinx formation than both wild-type (WT)NOS2+/+ andNOS2−/− controls. When we induced an in vivo chemical block in iNOS activity in p47phox−/− mice usingNG-monomethyl-l-arginine (L-NMMA), a large proportion of these mice eventually succumbed to opportunistic infections, but not before they resolved their chlamydial infections. Interestingly, when compared to WT and untreated p47phox−/− controls, L-NMMA-treated p47phox−/− mice resolved their infections more rapidly. However, L-NMMA-treated p47phox−/− mice lost resistance to chronic chlamydial disease, as evidenced by an increased rate of hydrosalpinx formation that was comparable to that forNOS2−/− mice. We conclude that phagocyte oxidase-derived reactive oxygen species (ROS) regulate RNS during chlamydial urogenital infection in the mouse. We further conclude that while neither phagocyte oxidase-derived ROS nor iNOS-derived RNS are essential for resolution of infection, RNS protect from chronic chlamydial disease in this model.
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