BLOOD SUBSTITUTES AND RETICULOENDOTHELIAL SYSTEM

这项拟议中的研究考察了两种潜在的血液 - Fluosol-DA（全氟化碳乳剂）， 无基质血红蛋白溶液--在网状内皮系统上 主要作用于库普弗细胞 网状内皮 系统对于主机防御至关重要，负责清除 血液中的外来微粒，例如细菌。 肝 巨噬细胞，库普弗细胞，清除大约95%的这些不必要的， 颗粒，因此是要集中的重要细胞。 巨噬细胞功能的三项指标-细菌清除 和细菌毒素（内毒素），杀灭细菌， 吞噬体运动的磁力测量-将是 在大鼠体内和离体灌注肝脏中进行评价。 这些 研究将在治疗后立即（1天）进行， Fluosol-DA或hemoglogin溶液，治疗后12天， 和治疗后3个月，以测量急性、短期和 对巨噬细胞功能的长期影响。 51Cr-内毒素和铜绿假单胞菌的清除将 在体内测量的全氟化合物和血红蛋白处理的 大鼠，以确定血液替代品对 整个网状内皮系统。 51Cr-内毒素清除率 和铜绿假单胞菌，然后将在分离的 灌注大鼠肝脏，以评估这些血液的影响 特别是库普弗细胞上的替代物 离体灌流 肝脏是研究枯否细胞的良好模型，因为它允许 保留的结构和生化功能的 体外肝脏。 磁力测量法，一种研究 巨噬细胞，测量细胞器的运动，并反映了国家的 细胞骨架 肝脏的磁力测量将 在体内和大鼠的离体灌注肝脏中进行1天， 治疗后12天和3个月。 因为细胞骨架 与吞噬作用有关，磁力测定法可能有助于理解 全氟碳化合物致枯否细胞功能障碍机制 血红蛋白处理的大鼠。

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.