MEDIATION OF ANTIBODY INDUCED GLOMERULAR INJURY

淀粉样蛋白A（AA）淀粉样变性，炎症性关节炎的并发症 结核病、麻风病和类风湿性关节炎等疾病， 随着未检查疾病的持续时间的增加而更频繁地发生。 AA原纤维来源于apoSAA蛋白（瞬时， 高密度脂蛋白（HDL）的损伤特异性成分）。 在 急性炎症发作消退，apoSAA升高 似乎通过两种途径分解代谢;一种是细胞相关的， 另一种涉及分泌的酶，无论是细胞外还是细胞内， 吞噬溶酶体 当正常清除受损时，不溶性AA 纤维在细胞外聚集。 在这里，我们研究apoSAA催化剂 当涉及AA淀粉样变性时，使用重组apoSAA 3和 非淀粉样蛋白生成亚型如apoSAA 1作为对照。 这些apoSAA 分子用于apoSAA的体内和体外研究 年轻人和老年人的肝细胞和巨噬细胞中的钙激活素， 淀粉样变和非淀粉样变，雄性和雌性仓鼠。 目标是 以在认为的体外系统中实现AA原纤维形成，从而 建立AA原纤维形成的必要因素。 的 假设apoSAA清除是其正常功能的一部分 阻断胆固醇逆向转运的方法正在测试中。 的 血脂和脂蛋白、血清淀粉样蛋白P（SAP） 和细胞外基质（ECM）成分，以改变能力， 用于完全催化apoSAA的溶酶体酶正在被 研究了 长期目标是提高正常 apoSAA在恢复体内平衡中的保护作用， 功能障碍，如淀粉样变性，发生的并发症， 随着年龄的增长， 并了解与年龄相关的变化是如何调节的， 蛋白水解可导致淀粉样原纤维形成。 电喷雾 电离及紫外、红外矩阵辅助激光器 解吸/电离已被用来验证分子量 并评估重组人apoSAA（MW 11，832 Da）和 模型肽的合成类似物，MW 2000-5000，其序列 代表SAA序列的关键部分。

Amyloid A (AA) amyloidosis, a complication of inflammatory diseases such as tuberculosis, leprosy and rheumatoid arthritis, occurs more frequently with increasing length of unchecked disease. AA fibrils are derived from apoSAA proteins (transient, injury-specific constituents of high density lipoprotein (HDL)). At the resolution of an acute inflammatory episode, elevated apoSAA appears to be catabolized by two pathways; one is cell-associated and theother involves secreted enzymes, either extracellularly or in phagolysosomes. When normal clearance is impaired, insoluble AA fibrils accumulate extracellularly. Here we study apoSAA catabolism as it relates to AA amyloidosis, using recombinant apoSAA3 and nonamyloidogenic isoforms such as apoSAA1 as controls. These apoSAA molecules are used for in vivo and in vitro studies of apoSAA catabolism in hepatocytes and macrophages from young and old, amyloidotic andnonamyloidotic, male and female hamsters. The goal is to achieve AA fibril formation in a deemed in vitro system, thereby establishing the requisite factors for AA fibril formation. The hypothesis that apoSAA clearance occurs as part of its normal function to interrupt reverse cholesterol transport is being tested. The ability of lipids and lipoproteins, serum amyloid P (SAP) andextracellular matrix (ECM) constituents to alter the capacity of lysosomal enzymes for complete catabolism of apoSAA is being investigated. The long range goals are to enhance the normal protective role of apoSAA in restoration of homeostasis, to prevent dysfunctions such as amyloidosis that occur as a complication of the chronic inflammatory conditions that are more prevalent with aging, and to understand in general how age-associated changes in regulated proteolysis can lead to amyloid fibril formation. Electrospray ionization and ultraviolet and infrared matrix-assisted laser desorption/ionization have been used to verify the molecular weights andevaluate purity of recombinant human apoSAA, MW 11,832 Da, and of synthetic analogs of model peptides, MWs 2000-5000, whose sequences represent key portions of the SAA sequence.