Role of complement and complement regulatory proteins in glomerulonephritis.
Role of complement and complement regulatory proteins in glomerulonephritis.
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补体和补体调节蛋白在肾小球肾炎中的作用。
DOI：
10.1007/s00281-002-0116-9
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Quigg,RichardJ
中科院分区：
文献类型：
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作者：
Quigg,RichardJ
补体系统由经典途径、旁路途径和甘露糖结合凝集素（MBL）途径组成，总共包含参与该系统的激活和调节的30多种蛋白质。从生理学的角度来看，补体系统在对微生物的免疫、免疫复合物的加工以及适当和最佳的细胞和体液免疫应答的发展中起作用。鉴于该系统的效力，天然调节剂存在于整个三个级联中，以防止对自身组织的不明智激活。毫不奇怪，由于肾小球持续暴露于血浆以及免疫复合物在影响肾小球的许多疾病过程中的明显作用，补体系统似乎在肾小球肾炎（GN）的发病机制中交织在一起。间接证据是肾小球肾炎患者的肾小球和尿液中存在补体激活产物。此外，在某些疾病状态下，如狼疮性肾炎、感染后GN和膜增生性GN，全身补体消耗是明显的[122]。最后，某些补体成分（如C1q和H因子）的遗传缺陷可导致肾小球病变[114，115]。实验动物模型进一步证明了补体系统在GN中的作用。20世纪60年代在狄克逊实验室进行的经典研究之后，由Alfreier、Matsuo、Salant和Wilson进行了研究，仅举几例[26，56]，这些研究确定了补体激活在各种疾病动物模型中的致病作用，包括膜性和系膜增生性GN（综述见[19，125]）。虽然会提到这些过去的研究，这篇评论将强调目前的进展可能与当代DNA技术，包括生产重组蛋白和转基因动物。这些研究使得在GN的背景下更彻底地放置补体系统。令临床医生兴奋的是，这些研究现在正流向GN患者的临床护理，这将在这里强调。
The complement system consists of the classical, alternative and mannose-binding lectin (MBL) pathways altogether containing over 30 proteins involved in the activation and regulation of this system. From a physiological standpoint, the complement system serves in immunity to microorganisms, the processing of immune complexes and in the development of an appropriate and optimal cellular and humoral immune response. Given the potency of this system, natural regulators are present throughout the three cascades to prevent injudicious activation on self tissues. Not surprisingly, because of the constant exposure of the glomerulus to plasma and the apparent role of immune complexes in many disease processes affecting the glomerulus, the complement system appears to be intertwined in the pathogenesis of glomerulonephritis (GN). Circumstantial evidence for this is the presence of complement activation products in glomeruli and urine of patients with GN. Furthermore, in some disease states, such as lupus nephritis, postinfectious GN, and membranoproliferative GN, systemic complement consumption is evident [122]. Lastly, genetic deficiencies of certain complement components, such as C1q and factor H, can result in glomerular pathology [114, 115].Further evidence for a role of the complement system in GN comes from experimental animal models. Classical studies done in the 1960s in the Dixon laboratories were followed by studies by Couser, Matsuo, Salant and Wilson, to name only a few [26, 56], which established a pathogenic role for complement activation in various animal models of disease, including membranous and mesangial proliferative GN (reviewed in [19, 125]). Although mention will be made of these past studies, this review will emphasize current advances made possible with contemporary DNA technology, including the production of recombinant proteins and genetically altered animals. These studies have allowed a more thorough placement of the complement system in the context of GN. Exciting to the clinician is that these studies are now flowing through to clinical care of patients with GN, as will be emphasized here.