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Am. J. Respir. Crit. Care Med., Volume 156, Number 1, July 1997, 223-228

Expression of Inducible Nitric Oxide Synthase by Macrophages in Rat Lung

HONG-WEN LIU, AMIT ANAND, KENNETH BLOCH, DAVID CHRISTIANI, and RICHARD KRADIN

Departments of Pathology and Medicine, Massachusetts General Hospital, Boston, Massachusetts

Nitric oxide (NO) is a short-lived free radical that is secreted by pulmonary macrophages (Mø). An inducible isoform of NO synthase (iNOS) catalyses the production of NO and is activated by lipopolysaccharide and certain T-helper(h) 1 cytokines, including interferon-gamma and TNF-alpha . In the present study, iNOS+ interstitial cells were demonstrated in the alveolar wall of normal Lewis rat lung. Enzymatic digests of normal lung showed that approximately one third of pulmonary ED1+ interstitial Mø (IM) were iNOS+ and secreted modest amounts of NO without ex vivo stimulation, whereas normal alveolar macrophages (AM) were iNOS- and showed no basal NO secretion. When incubated with heat-killed Listeria monocytogenes (HKL) in vitro, AM secreted larger amounts of NO than did IM. Recombinant murine GM-CSF stimulated production of NO by AM but not by IM. However, when IM were costimulated with GM-CSF and IFN-gamma , they expressed a marked increase in NO production. Intratracheal challenge with HKL yielded decreased NO production by IM. We conclude that iNOS+ IM are present in normal rat lung, where they regulate the pulmonary cell-mediated immune response to antigen.




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