Response of alveolar macrophages from inducible nitric oxide synthase knockout or wild-type mice to an in vitro lipopolysaccharide or silica exposure.

The role of nitric oxide (NO) in pulmonary disease has been controversial with both antiinflammatory (scavenging radicals and inhibiting NF-eB activation) and proinflammatory (forming highly reactive peroxynitrite and augmenting NF-eB activation by inflammatory agents) actions reported. Therefore, a study has been initiated to determine whether deletion of the inducible nitric oxide synthase (iNOS) gene in the C57BL/6J mouse alters the pulmonary macrophage response to lipopolysaccharide (LPS) or silica. The objective of the initial phase of this study was to determine the difference in responsiveness of alveolar macrophages (AMs), harvested from naive wild-type (WT) or iNOS knockout (iNOS KO) mice, to an in vitro LPS or silica exposure. Primary AMs were obtained by bronchoalveolar lavage (BAL) from age- and weightmatched iNOS KO and WT mice. The cells were treated with interferon-gamma (IFN-a) (50 U/ml), IFN-a (50 U/ml) + LPS (1 µg/ml), LPS (0.01-100 µg/ml), or silica (25-250 µg/ml). The following paramet...