Although some studies suggest that several pollutant gases inhibit pulmonary macrophage phagocytosis, the mechanism mediating this inhibition is unknown. We have developed new techniques to investigate phagocytosis. These include the ability to distinguish and quantitate bound versus ingested particles as well as the ability to evaluate the heterogeneity of these and other characteristics within the pulmonary macrophage population. Using a combination of in vivo and in vitro experiments, we propose to delineate the mechanism by which two pollutant gases, ozone (03) and nitrogen dioxide (NO2) affect the phagocytosis of immunologically unopsonized particles. In one series of experiments we will evaluate the effects of 03 and N02 on the phagocytic capability of individual macrophages within the exposed cell population. The uptake of green fluorescent latex particles coated with albumin will be quantitated using flow cytometry. The differentiation of attached versus ingested particles will be made utilizing rhodamine conjugated antibodies to the particle surface. We will also evaluate the effects of these gases on the age distribution of resident macrophages. Macrophage age will be determined by quantitating the amount of an age-related cell surface antigen specific to pulmonary macrophages. Since both gases elicit an inflammatory response, another series of experiments will evaluate the effects of inflammatory agents on phagocytosis. These agents will be used to explore the roles of intracellular calcium and cyclic cAMP in phagocytosis and will facilitate our continuing effort to define factors which regulate phagocytic function. The integration of this information will enhance our understanding of how phagocytosis is affected in vivo by pollutant gases and other inflammatory agents.
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