EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE BY MACROPHAGES IN RAT LUNG

Nitric oxide (NO) is a short-lived free radical that is secreted by pu lmonary macrophages (Mo). An inducible isoform of NO synthase (iNOS) c atalyses the production of NO and is activated by lipopolysaccharide a nd certain T-helper(h) 1 cytokines, including interferon-gamma and TNF -alpha. In the present study, iNOS(+) interstitial cells were demonstr ated in the alveolar wall of normal Lewis rat lung. Enzymatic digests of normal lung showed that approximately one third of pulmonary ED1(+) interstitial Mo (IM) were iNOS(+) and secreted modest amounts of NO w ithout ex vivo stimulation, whereas normal alveolar macrophages (AM) w ere iNOS(-) and showed no basal NO secretion. When incubated with heat -killed Listeria monocytogenes (HKL) in vitro, AM secreted larger amou nts of NO than did IM. Recombinant murine CM-CSF stimulated production of NO by AM hut not by IM. However, when IM were costimulated with CM -CSF and IFN-gamma, they expressed a marked increase in NO production. Intratracheal challenge with HKL yielded decreased NO production by I M. We conclude that iNOS(+) IM are present in normal rat lung, where t hey regulate the pulmonary cell-mediated immune response to antigen.