Morgan B P, Luzio J P, Campbell A K
Cell Calcium. 1986 Dec;7(5-6):399-411. doi: 10.1016/0143-4160(86)90042-4.
Disturbances in intracellular Ca2+ are known to be important in cell injury caused by a wide range of toxic factors. The complement system is a major effector of immune damage in vivo, and is known to be involved in the pathogenesis of many immune diseases. We present here evidence that the potentially lethal membrane attack complex of complement causes a rapid increase in intracellular free Ca2+ concentration before any other detectable biochemical changes in the cell. In nucleated cells the increased intracellular free Ca2+ concentration initially stimulates recovery processes, allowing the cell to escape mild complement attack and also activates the production of inflammatory mediators, which may amplify an ongoing inflammatory response. More severe complement membrane attack causes a more rapid rise in intracellular free Ca2+ concentration allowing a threshold to be breached above which recovery processes are overwhelmed, and cell death occurs. The importance of non-lytic effects and recovery processes mediated by Ca2+, and the molecular basis of these effects are discussed, and the hypothesis proposed that the cell-injuring effects of other "pore-forming" toxins are also caused by increases in intracellular free Ca2+.
细胞内钙离子紊乱在多种毒性因子所致的细胞损伤中起着重要作用。补体系统是体内免疫损伤的主要效应因子，已知其参与多种免疫疾病的发病机制。我们在此提供证据表明，补体具有潜在致死性的膜攻击复合物会在细胞内任何其他可检测到的生化变化之前，迅速提高细胞内游离钙离子浓度。在有核细胞中，细胞内游离钙离子浓度升高最初会刺激恢复过程，使细胞能够逃脱轻度补体攻击，同时还会激活炎症介质的产生，这可能会放大正在进行的炎症反应。更严重的补体膜攻击会使细胞内游离钙离子浓度上升更快，从而突破一个阈值，超过该阈值后恢复过程就会不堪重负，细胞死亡。本文讨论了由钙离子介导的非溶细胞效应和恢复过程的重要性以及这些效应的分子基础，并提出假说认为其他“成孔”毒素对细胞的损伤作用也是由细胞内游离钙离子浓度升高引起的。
