Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase

Michael U. Shiloh, John D. MacMicking, Susan Nicholson, Juliet E. Brause, Strite Potter, Michael Marino, Ferric Fang, Mary Dinauer, Carl Nathan

Research output: Contribution to journalArticle

393 Scopus citations

Abstract

The two genetically established antimicrobial mechanisms of macrophages are production of reactive oxygen intermediates by phagocyte oxidase (phox) and reactive nitrogen intermediates by inducible nitric oxide synthase (NOS2). Mice doubly deficient in both enzymes (gp91(phox-/-)/NOS2(-/-) formed massive abscesses containing commensal organisms, mostly enteric bacteria, even when reared under specific pathogen-free conditions with antibiotics. Neither parental strain showed such infections. Thus, phox and NOS2 appear to compensate for each other's deficiency in providing resistance to indigenous bacteria, and no other pathway does so fully. Macrophages from gp91(phox-1- )/NOS2(-/-) mice could not kill virulent Listeria. Their killing of S. typhimurium, E. coli, and attenuated Listeria was markedly diminished but demonstrable, establishing the existence of a mechanism of macrophage antibacterial activity independent of phox and NOS2.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalImmunity
Volume10
Issue number1
DOIs
StatePublished - Jan 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Shiloh, M. U., MacMicking, J. D., Nicholson, S., Brause, J. E., Potter, S., Marino, M., Fang, F., Dinauer, M., & Nathan, C. (1999). Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase. Immunity, 10(1), 29-38. https://doi.org/10.1016/S1074-7613(00)80004-7