Complement and autoimmune glomerular diseases.
Complement and autoimmune glomerular diseases.
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DOI：
10.1159/000075692
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
R. Quigg
中科院分区：
文献类型：
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作者：
R. Quigg
肾小球是肾脏中的特殊结构，负责在人类每天产生超过150升的血浆超滤液。这种结构的某些特征有利于参与自身免疫性疾病。肾小球中免疫复合体的形成，无论是从循环中沉积还是在原位产生，都可以激活补体系统。该系统的活性产物包括与免疫复合物共价结合的过敏性毒素C3a和C5a，以及C5b-9膜攻击复合体。如果补体在血液成分可接触到的部位被激活，例如在内皮下和系膜区域，产生的C3a、C5a和C3b可以与它们各自的炎症细胞上的受体相互作用，导致渗出性损害。此外，承载相关受体的固有肾小球细胞也可能被激活并增殖，从而参与炎症反应。在特殊部位，如上皮下区，补体激活产物不能被血细胞获得，因此，由此产生的病理是非炎症性的。在这种情况下，C5b-9的作用占主导地位，包括通过尚不完全表征的途径激活和损伤细胞。现在有多种方法可以改变补体途径，包括抗体抑制剂和基于自然产生的补体调节剂的重组蛋白。这些药物的使用，以及补体系统个别成分被删除的小鼠，使人们对补体系统如何参与肾小球疾病有了很大的了解。操纵补体途径的能力现在在临床环境中是现实的，但决定性的人体研究很难实现。
The renal glomerulus is the specialized structure in the kidney responsible for generating over 150 liters of plasma ultrafiltrate per day in humans. Certain characteristics of this structure favor involvement in autoimmune diseases. Formation of immune complexes in the glomerulus, either deposited from the circulation or generated in situ, can activate the complement system. Active products of this system include the anaphylatoxins C3a and C5a, C3b, which covalently associates with immune complexes, and the C5b-9 membrane attack complex. If complement is activated in a site accessible to blood constituents, such as in the subendothelial and mesangial regions, generated C3a, C5a and C3b can interact with their respective receptors on inflammatory cells to lead to an exudative lesion. In addition, intrinsic glomerular cells bearing relevant receptors may also be activated and can proliferate to contribute to the inflammation. In a privileged site such as the subepithelial region, complement activation products are not accessible to blood cells, and as such, the resultant pathology is noninflammatory. In this setting, effects of C5b-9 predominate, which include activation and injury of cells through still incompletely characterized pathways. Various means to alter the complement pathway are now available, including antibody inhibitors and recombinant proteins based upon naturally occurring complement regulators. The use of these agents, as well as mice in which individual components of the complement system have been deleted, has given a great deal of insight into how the complement system is involved in glomerular disease. The ability to manipulate the complement pathway is now a reality in a clinical setting, yet conclusive human studies are difficult to achieve.