SURFACTANT MEDIATION OF OXIDANT-INDUCED INFLAMMATION

DESCRIPTION Exposure to nitrogen dioxide (NO2) is characterized by rapidly increasing levels of inflammatory mediators and inflammatory cells. There is also a rapid inhibition of the surface active properties of surfactant and changes in the levels and nature of some surfactant components, including increased levels of surfactant-associated protein-A (SP-A). The central hypothesis of this proposal is that exposure to NO2 causes changes in surfactant and its constituents, including SP-A. These changes then trigger and enhance inflammation, causing functional and structural changes that can result in or contribute to pulmonary disease. In addition, the ability of SP-A to increase production of reactive oxidant species may contribute to the inflammatory state resulting from the initial exposure to NO2. The mechanism(s) responsible for these actions will be investigated by analyzing the composition of surfactant subfractions and their constituents after exposure to NO2. The treated surfactant constituents will then be tested for their ability to modulate TNF-alpha and IL-8 protein and mRNA production by a macrophage cell line. These will be measured by ELISA and mRNA dot blotting. The direct effect of NO2 on these cells will then be assessed by exposing the cells to NO2 and measuring their production of TNF-alpha and IL-8 in response to other inflammatory stimuli.