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

M U Shiloh; J D MacMicking; S Nicholson; J E Brause; S Potter; M Marino; F Fang; M Dinauer; C Nathan

doi:10.1016/s1074-7613(00)80004-7

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

Immunity. 1999 Jan;10(1):29-38. doi: 10.1016/s1074-7613(00)80004-7.

Authors

M U Shiloh¹, J D MacMicking, S Nicholson, J E Brause, S Potter, M Marino, F Fang, M Dinauer, C Nathan

Affiliation

¹ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York 10021, USA.

PMID: 10023768
DOI: 10.1016/s1074-7613(00)80004-7

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-/-)/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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Abscess / genetics
Abscess / immunology
Animals
Bacterial Infections / genetics
Bacterial Infections / immunology
Crosses, Genetic
Escherichia coli / immunology
Genetic Predisposition to Disease
Listeria monocytogenes / immunology
Listeriosis / genetics
Listeriosis / immunology
Macrophages, Peritoneal / enzymology*
Macrophages, Peritoneal / immunology*
Macrophages, Peritoneal / microbiology
Membrane Glycoproteins / deficiency*
Membrane Glycoproteins / genetics
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
NADPH Oxidase 2
NADPH Oxidases / deficiency*
NADPH Oxidases / genetics
Nitric Oxide Synthase / deficiency*
Nitric Oxide Synthase / genetics
Nitric Oxide Synthase Type II
Phenotype
Salmonella Infections, Animal / genetics
Salmonella Infections, Animal / immunology
Salmonella typhimurium / immunology

Substances

Membrane Glycoproteins
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nos2 protein, mouse
CYBB protein, human
NADPH Oxidase 2
NADPH Oxidases

Grants and funding

etc