MECHANISMS OF COMPLEMENT ATTACK ON NUCLEATED CELLS

红细胞和人工脂双分子层在许多方面的研究 实验室已经发现了膜的基本特征 补体攻击机制(C)。因此，我们的 在过去的几年里，研究致力于 对C介导的细胞死亡机制的理解(S) 代谢活跃的有核细胞(NC)。我们发现， NC的细胞溶解需要多个C5b-9通道，因为 细胞在有限C攻击下存活的防御机制 消除潜在的裂解C通道。此外， 通道，当以次要的数字存在时，会导致瞬变 增加细胞内钙离子并发挥多种生物学效应 如激活磷脂酶、脂甲基转移酶，以及 细胞中的中性蛋白酶。我们节目的目的是学习 C5b-9介导细胞死亡、刺激 细胞修复有限的损伤，并调节细胞功能 与靶细胞的病理生理学有关 炎症和免疫力。 具体地说，我们想确定C诱导的生化 刺激修复过程的信号。我们还将调查 其余通道引起的细胞死亡是否完全 依赖于胶体渗透放松管制，如果适用的话 细胞的代谢过程中涉及哪些代谢途径 死亡。此外，我们将检查新陈代谢是否 刺激与C5b-9类似的修复过程 在通过形成通道进行有限攻击后的目标中也会发生这种情况 来源于CTL或NK细胞的蛋白质。我们将继续研究 C8结合蛋白的结构和功能 同源C5b-在有核细胞杀伤和刺激中的作用 9. 总而言之，这些研究将显著增加我们的 对补体通道生物学活性的认识 和其他在NC靶点上形成免疫效应器的通道。

Studies with erythrocytes and artificial lipid bilayers in many laboratories have yielded the fundamental features of membrane attack mechanisms by complement (C). Consequently, our research during the last few years has been devoted to understanding the mechanism(s) of C-mediated cell death in metabolically active nucleated cells (NC). We have found that cytolysis of NC requires multiple C5b-9 channels, due to the defense mechanism of the cell to survive limited C attack by eliminating the potentially lytic C channels. In addition, the channels, when present in sublytic numbers, cause a transient increase in cellular Ca2+ and exert a variety of biological effects such as activation of phospholipases, lipid methyltransferases, and neutral proteases in the cell. Our program is aimed at studying the mechanisms by which C5b-9 mediates cell death, stimulates the cell to repair limited injury, and modulates cellular functions that are relevant to the pathophysiology of the target cells in inflammation and immunity. Specifically, we want to determine the C-induced biochemical signals that stimulate the repair process. We will also investigate whether cell death elicited by the remaining channels is entirely dependent on colloid-osmotic deregulation, and if applicable which metabolic pathways are involved in the process of cell death. In addition, we will examine whether metabolic stimulation of repair processes similar to those produced by C5b-9 also occur in targets following limited attack by channel-forming proteins derived from CTL or NK-cells. We will continue to study the structure and functional aspects of C8-binding protein, and its role in nucleated cell killing and stimulation by homologous C5b- 9. These studies, collectively, will significantly increase our knowledge on the biological activities of complement channels and other channel forming immune effectors on NC targets.