The object of this proposal is to study the impact of silica on some of the major functions of the alveolar macrophage, namely, phagocytosis and bactericidal activity against particles and bacteria. Related and specific functions to be studied include spreading, adherence, chemotaxis, Fc receptor activity and the release of oxygen products after stimulation with formyl methionyl peptides; the latter are considered products of bacterial metabolism. These functions will be correlated with the amount of ingested silica, utilizing scanning electron microscopy coupled with energy dispersive electron probe analysis. These aveolar macrophage functions will be determined after short-term in vitro exposure and also in macrophages recovered at varying time points from experimental animals which have been exposed to silica in vivo. Most of these alveolar macrophage activities are linked to receptors and enzymes which are located near or at the plasma membrane. In order to elucidate molecular mechanisms of injury to alveolar macrophages, we will test the hypothesis that silica injures cell and subcellular membranes of the alveolar macrophage by lipid peroxidation of unsaturated lipid in the membrane; and this in turn results in a physical change (membrane fluidity) of the membrane which impairs the normal functioning of relevant receptors and enzyme systems. Lipid integrity of alveolar macrophage membranes will be determined by fluorescence anisotropy.
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