Expression of inducible nitric oxide synthase by macrophages in rat lung.
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.
Liu
H W
HW
Department of Pathology, Massachusetts General Hospital, Boston 02114, USA.
Anand
A
A
Bloch
K
K
Christiani
D
D
Kradin
R
R
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008089:Listeria monocytogenes / Q000276:immunology; D016676:Macrophages, Alveolar / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis*; D051381:Rats; D011917:Rats, Inbred Lew
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase