Pulmonary surfactant inhibits LPS-induced nitric oxide production by alveolar macrophages

The objectives of this investigation were 1) to report that pulmonary surfa ctant inhibits lipopolysaccharide (LPS)induced nitric oxide (.NO) productio n by rat alveolar macrophages, 2) to study possible mechanisms for this eff ect, and 3) to determine which surfactant component(s) is responsible. .NO produced by the cells in response to LPS is due to an inducible .NO synthas e (iNOS). Surfactant inhibits LPS-induced .NO formation in a concentration- dependent manner; .NO production is inhibited by similar to-50 and similar to 75% at surfactant levels of 100 and 200 mu g phospholipid/ml, respective ly. The inhibition is not due to surfactant interference with the interacti on of LPS with the cells or to disruption of the formation of iNOS mRNA. Al so, surfactant does not seem to reduce .NO formation by directly affecting INOS activity or by acting as an antioxidant or radical scavenger. However, in the presence of surfactant, there is an similar to 80% reduction in the amount; of LPS-induced iNOS protein in the cells. LPS-induced .NO producti on is inhibited by Survanta, a surfactant preparation used in replacement t herapy, as well as by natural surfactant. .NO formation is not affected by the major lipid components of surfactant or by two surfactant-associated pr oteins, surfactant protein (SP) A or SP-C. However, the hydrophobic SP-B in hibits NO formation in a concentration-dependent manner; .NO production is inhibited by similar to 50 and similar to 90% at SP-B levels of 1-2 and 10 mu g/ml, respectively. These results show that lung surfactant inhibits LPS -induced .NO production by alveolar macrophages, that the effect is due to a reduction in iNOS protein levels, and that the surfactant component respo nsible for the reduction is SP-B.