Differential expression of inducible nitric oxide synthase gene by alveolar and peritoneal macrophages in lipopolysaccharide-hyporesponsive C3H/HeJ mice.

Abstract

In lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, alveolar macrophages (AMphi) produce much more tumour necrosis factor-alpha than peritoneal macrophages (PMphi) when stimulated with LPS (10 microgram/ml), but the induction of inducible nitric oxide synthase (iNOS) gene expression and production of nitric oxide (NO) in AMphi are not found. In the present study, we determined the induction of iNOS gene expression, using semi-quantitative reverse transcription-polymerase chain reaction, and the release of NO in AMphi and PMphi from C3H/HeJ and C3H/HeN mice. The results showed the induction of iNOS mRNA accumulation in a dose-dependent manner by LPS alone or in combination with interferon-gamma in both macrophages. The effects of the stimuli on iNOS gene expression and NO production were significantly higher in AMphi than in the PMphi of C3H/HeJ mice. The response of macrophages from C3H/HeN mice was similar to those from C3H/HeJ mice, but the difference of iNOS gene expression between AMphi and PMphi in C3H/HeN mice was not as striking as in C3H/HeJ mice. The results show that the iNOS gene expression and NO production were activated differently in AMphi and PMphi and suggest that the functional properties of macrophages isolated from distinct origins are different.