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. 1993 Feb;61(2):491–497. doi: 10.1128/iai.61.2.491-497.1993

Gamma interferon-induced nitric oxide production reduces Chlamydia trachomatis infectivity in McCoy cells.

J Mayer 1, M L Woods 1, Z Vavrin 1, J B Hibbs Jr 1
PMCID: PMC302755  PMID: 8423078

Abstract

McCoy cells, murine-derived cells commonly used for propagation of chlamydiae, were found to be efficient producers of nitric oxide (NO) when primed with murine gamma interferon (IFN-gamma) and then exposed to the second signals provided by Escherichia coli lipopolysaccharide, human interleukin-1 alpha, murine tumor necrosis factor alpha, or Chlamydia trachomatis type H. Murine recombinant IFN-gamma over a range of 0 to 50 U/ml inhibited infectivity of C. trachomatis type H in a dose-dependent fashion in McCoy cells while simultaneously inducing NO production. Quantitation of infectious chlamydia progeny remaining in McCoy cells 48 or 72 h postinfection revealed that IFN-gamma-primed McCoy cells reduced chlamydial inclusion-forming units (expressed as units per milliliter) by 4 log10 units at higher IFN-gamma concentrations (50 U/ml) compared with control values. The magnitude of this antichlamydial effect was directly related to increased synthesis of NO, the production of which was IFN-gamma dose dependent. The antichlamydial effects of IFN-gamma were blocked in a dose-dependent manner by the addition of N-guanidino-monomethyl L-arginine (MLA), an inhibitor of nitric oxide synthesis. These results suggest that although IFN-gamma priming of McCoy cells is required for antichlamydial activity, nitric oxide is a necessary effector molecule involved in the mechanism(s) of IFN-gamma-induced inhibition of chlamydial proliferation in this murine cell line. The ability to block the potent antichlamydial effects of IFN-gamma by inhibition of a specific enzyme, nitric oxide synthase, may give insights into mechanisms by which IFN-gamma and perhaps other cytokines are able to control proliferation of chlamydiae and other intracellular pathogens.

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Selected References

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