BLOOD SUBSTITUTES AND RETICULOENDOTHELIAL SYSTEM

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The proposed study examines the effects of two potential blood substitutes -- Fluosol-DA (a perfluorocarbon emulsion) and stroma-free hemoglobin solution -- on Reticuloendothelial system function with a focus on Kupffer cells. The Reticuloendothelial system is critical for host defense and is responsible for clearance of foreign particulates, e.g. bacteria, from the blood. Liver macrophages, Kupffer cells, clear about 95% of these unwanted particulates and thus are important cells on which to concentrate. Three measures of macrophage function - clearance of bacteria and bacteria toxin (endotoxin), killing of bacteria, and magnetometric measures of phagosomal motion - will be evaluated in rats in vivo and in the isolated perfused liver. These studies will be done immediately (1 day) after treatment with either Fluosol-DA or hemoglogin solution, 12 days post-treatment, and 3 months post-treatment to measure acute, short term, and longer term effects on macrophage function, respectively. Clearance of 51Cr-endotoxin and pseudomonas aeruginosa will be measured in vivo in perfluorochemical- and hemoglobin-treated rats to determine the effects of the blood substitutes on the entire Reticuloendothelial system. Clearance of 51Cr-endotoxin and pseudomonas aeruginosa will then be measured in the isolated perfused rat liver to evaluate the effects of these blood substitutes on Kupffer cells specifically. The isolated perfused liver is a good model for studying Kupffer cells since it allows for the retention of the structure and biochemical functioning of the liver in vitro. Magnetometry, a novel approach to studying macrophages, measures organelle motion and reflects the state of the cytoskeleton. Magnetometric measurements of the liver will be done in vivo and in the isolated perfused liver in rats at 1 day, 12 days, and 3 months post-treatment. Since the cytoskeleton is involved in phagocytosis, magnetometry may aid in understanding the mechanism of Kupffer cell dysfunction in perfluorocarbon-and hemoglobin-treated rats.