MECHANISM OF COMPLEMENT ATTACK ON NUCLEATED CELLS

作为对红细胞和人工脂双层的研究结果 许多实验室认为，膜攻击的基本特征是 补语现在已经很好地理解了。因此，我们在这一时期的研究 过去的一年转向补体攻击机制的研究(S) 新陈代谢活跃的有核细胞。这一转变的动机是 事实上，这些细胞直接参与了生理和 补体的病理活动，以及认识到有 我们对补体攻击有核细胞的认识存在很大差距 尊重其机制(S)和后果。因此，我们的节目是 旨在研究汉语补语通道的特点 有核细胞的膜，特别是它们的稳定性和调节 某些药物和激素的作用与细胞容量的关系 用于膜合成。我们计划研究的其他重要问题 代谢因素在补体介导的细胞死亡中的作用 补体与细胞相互作用过程中膜酶的调节 膜。这些包括钙离子流经通道的作用。 补体介导和磷脂酶介导的细胞死亡及其机制 激活及其后果。具体地说，我们希望确定：(1) 补体介导的细胞死亡表现为单次攻击还是多次攻击 特征，(2)是否补充有核细胞中的通道 膜是稳定的，(3)如何改变膜脂合成的试剂 影响对补体介导的细胞毒性的易感性，(4)如何 补体激活膜相关磷脂酶，以及(5) 细胞膜的组成是物种限制的原因 关于C9的溶解功能。总体而言，我们期望 研究将显著增加我们对细胞毒性和 补体在免疫和变态反应中的炎症活性

As a result of studies with erythrocytes and artificial lipid bilayers in many laboratories, the fundamental features of membrane attack by complement are now well understood. Consequently, our research during the past year has shifted to studies of the mechanism(s) of complement attack on metabolically active nucleated cells. This shift is motivated by the fact that such cells are directly involved in the physiological and pathological activities of complement, and the recognition that there are large gaps in our knowledge of complement attack on nucleated cells with respect to its mechanism(s) and consequences. Accordingly, our program is aimed at studying the characteristics of complement channels in the membranes of nucleated cells, especially their stability and the modulating effect of certain drugs and hormones, in relation to the cell's capacity for membrane synthesis. Other important issues we plan to study concern the role of metabolic factors in complement-mediated cell death, and the modulation of membrane enzymes during complement interaction with cell membranes. These include the role of calcium flux through the channels in cell death and the mechanism complement-mediated and phospholipase activation and its consequences. Specifically, we want to determine: (1) Whether complement-mediated cell death exhibits single-hit or multi-hit characteristics, (2) whether complement channels in the nucleated cell membrane are stable, (3) how agents that alter membrane lipid synthesis affect the susceptibility to complement-mediated cytotoxicity, (4) how complement activates membrane-associated phospholipase, and (5) which constituent of the cell membrane is responsible for the species restriction with respect to the lytic function of C9. Collectively, we expect that studies will significantly increase our knowledge of the cytotoxic and inflammatory activities of complement in immunity and allergy.