Constitutive nitric oxide production by rat alveolar macrophages.
Miles-PR; Bowman-L; Rengasamy-A; Huffman-L
Am J Physiol, Lung Cell Mol Physiol 1998 Mar; 274(3 Pt 1):L360-L368
Results from previous studies suggest that alveolar macrophages must be exposed to inflammatory stimuli to produce nitric oxide (NO). In this study, we report that naive unstimulated rat alveolar macrophages do produce NO and attempt to characterize this process. Western blot analysis demonstrates that the enzyme responsible is an endothelial nitric oxide synthase (eNOS). No brain or inducible NOS can be detected. The rate of NO production is approximately 0.07 nmol.10(6) cells-1.h-1, an amount that is less than that produced by the eNOS found in alveolar type II or endothelial cells. Alveolar macrophage NO formation is increased in the presence of extracellular L-arginine, incubation medium containing magnesium and no calcium, a calcium ionophore (A-23187), or methacholine. NO production is inhibited by NG-nitro-L-arginine methyl ester (L-NAME) but not by NG-nitro-L-arginine, L-N5-(1-iminomethyl)ornithine hydrochloride, or aminoguanidine. Incubation with ATP, ADP, or histamine also inhibits NO formation. Some of these properties are similar to and some are different from properties of eNOS in other cell types. Cellular NO levels do not appear to be related to ATP or lactate content. Alveolar macrophage production of NO can be increased approximately threefold in the presence of lung surfactant or its major component, dipalmitoyl phosphatidylcholine (DPPC). The DPPC-induced increase in NO formation is time and concentration dependent, can be completely inhibited by L-NAME, and does not appear to be related to the degradation of DPPC by alveolar macrophages. These results demonstrate that unstimulated alveolar macrophages produce .NO via an eNOS and that lung surfactant increases NO formation. This latter effect may be important in maintaining an anti-inflammatory state in vivo.
Laboratory-animals; Animals; Animal-studies; Exposure-levels; Magnesium-compounds; In-vivo-studies; Lung-function; Lung-cells;
Author Keywords: lung surfactant; dipalmitoyl phosphatidylcholine; nitric oxide synthase
P. R. Miles, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown 26505
American Journal of Physiology: Lung Cellular and Molecular Physiology