MODULATION OF EXPERIMENTAL ARTHRITIS IN MICE BY GPI-ANCHORED PROTEIN TRANSFER

小鼠中的胶原诱导的关节炎（CIA）是一种实验模型， 类风湿性关节炎（RA），密切模仿人类疾病， 临床上和免疫病理学上。与人类RA一样， 疾病映射到II类MHC的亚区（I-A）， 软骨II型胶原蛋白由T细胞介导和体液介导 免疫机制最近出现的大量证据表明， 有一类细胞表面蛋白具有不寻常的特性， 以及在体内，能够从一种细胞类型转移到另一种细胞类型。的 具有这种能力的蛋白质是膜蛋白质， 由肌醇磷脂（GPI）单元锚定。重要的是 此外，还证明这些蛋白质在纯化和 直接添加到细胞中，插入到目标细胞中， ，功能齐全。这类蛋白质包括 体液免疫攻击的两个关键抑制剂[加速衰变 因子（CD 55）和反应性溶解的膜抑制因子（MIRL） 或CD 59]。通过重组DNA技术，已经表明它是 有可能重新设计体液和细胞的其他关键调节因子， 免疫攻击，从而拥有GPI锚。该可行性研究是 旨在研究新的实验方法，以提供这些GPI- 含有调节剂的关节炎， 表达蛋白质和纯化的蛋白质本身。数据 可能与RA和其他疾病的新治疗方式有关。 风湿性疾病

Collagen-induced arthritis (CIA) in mice is an experimental model of rheumatoid arthritis (RA) that closely mimics the human disorder both clinically and immunopathologically. As in human RA, susceptibility to the disease maps to a subregion (the I-A) of class II MHC and injury to cartilage type II collagen results from both T cell-mediated and humoral immune mechanisms. A recently emerging body of evidence has indicated that one class of cell surface proteins has the unusual property, both in vitro and in vivo, of being able to transfer from one cell type to another. The proteins that possess this capability are proteins that are membrane- anchored by glycoinositolphospholipid (GPI) units. Importantly, it additionally has been demonstrated that these proteins, when purified and added directly to cells, insert themselves into the target cells, and once incorporated, are fully functional. Among the proteins in this class are two critical inhibitors of humoral immune attack [the decay accelerating factor (DAF) or CD55 and the membrane inhibitor of reactive lysis (MIRL) or CD59]. By recombinant DNA technology, it has been shown that it is possible to re-engineer other key regulators of humoral and cellular immune attack so as to possess GPI anchors. This feasibility study is directed at examining new experimental methods for delivery of these GPI- containing regulators to inflamed joints using both transgenic animals expressing the proteins and the purified proteins themselves. The data obtained could have relevance to new treatment modalities for RA and other rheumatic diseases.