Inducible nitric oxide synthase of macrophages. Present knowledge and evidence for species-specific regulation.
An important mechanism by which macrophages (M phi) halt the growth of and eliminate a broad array of intracellular pathogens is the production of nitric oxide (NO). NO generation is catalyzed by inducible nitric oxide synthase (iNOS) converting arginine into citrulline and NO. In murine M phi, iNOS activity is regulated largely at the transcriptional level. LPS and IFN-gamma induce iNOS, IL-4 and TGF-beta down-regulate LPS or IFN-gamma induced iNOS. In human M phi, iNOS cannot be induced by conventional activating regimes in vitro. We studied iNOS induction in ruminant monocytes and M phi from various sources (bone marrow, alveolar lavage, peripheral blood) and found that there is a species-specific and differentiation stage-dependent pattern of iNOS regulation in vitro. Notably, cattle M phi and monocytes respond to distinct signals by iNOS expression. Goat monocytes and M phi resemble human, pig and rabbit M phi in that upon treatment with conventional activating stimuli, they express less iNOS than unstimulated murine or bovine M phi and fail to generate detectable amounts of nitrite and nitrate.
Jungi
T W
TW
Institute of Veterinary Virology, University of Berne, Switzerland.
Adler
H
H
Adler
B
B
Thöny
M
M
Krampe
M
M
Peterhans
E
E
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D015536:Down-Regulation / Q000502:physiology*; D006041:Goats; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D011817:Rabbits; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology*
D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase