INDUCIBLE NITRIC OXIDE SYNTHASE OF MACROPHAGES. PRESENT KNOWLEDGE AND EVIDENCE FOR SPECIES-SPECIFIC REGULATION

Abstract An important mechanism by which macrophages (Mφ) 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 Mφ, iNOS activity is regulated largely at the transcriptional level. LPS and IFN-γ induce iNOS, IL-4 and TGF-β down-regulate LPS or IFN-γ induced iNOS. In human Mφ, iNOS cannot be induced by conventional activating regimes in vitro . We studied iNOS induction in ruminant monocytes and Mφ 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 Mφ and monocytes respond to distinct signals by iNOS expression. Goat monocytes and Mφ resemble human, pig and rabbit Mφ in that upon treatment with conventional activating stimuli, they express less iNOS than unstimulated murine or bovine Mφ and fail to generate detectable amounts of nitrite and nitrate.