TY - JOUR
T1 - Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase
AU - Shiloh, Michael U.
AU - MacMicking, John D.
AU - Nicholson, Susan
AU - Brause, Juliet E.
AU - Potter, Strite
AU - Marino, Michael
AU - Fang, Ferric
AU - Dinauer, Mary
AU - Nathan, Carl
N1 - Funding Information:
We thank L. Old for encouragement and support, R. North and D. Portnoy for advice and bacterial strains, N. Lipman and S. Perkins for advice on animal husbandry, Genentech for a gift of cytokines, and D. Marciano for critique of the manuscript. This work was supported by National Institutes of Health grants HL51967, AI34543, and GM53921 to C. N., HL52565 to M. D., AI39557 to F. F., and a Medical Scientist Training Program Grant GM07739 fellowship and Iris L. and Leverett S. Woodward Medical Scientist Fellowship to M. U. S.
PY - 1999/1
Y1 - 1999/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0032984248
U2 - 10.1016/S1074-7613(00)80004-7
DO - 10.1016/S1074-7613(00)80004-7
M3 - Article
C2 - 10023768
AN - SCOPUS:0032984248
SN - 1074-7613
VL - 10
SP - 29
EP - 38
JO - Immunity
JF - Immunity
IS - 1
ER -