Regulation of complement C3 and C4 synthesis in human peritoneal mesothelial cells by peritoneal dialysis fluid
Regulation of complement C3 and C4 synthesis in human peritoneal mesothelial cells by peritoneal dialysis fluid
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DOI：
10.1111/j.1365-2249.2004.02407.x
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发表时间：
2004-04-01
影响因子：
4.6
通讯作者：
Sacks, SH
中科院分区：
文献类型：
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作者：
Tang, S;Leung, JCK;Sacks, SH
尽管补体在慢性腹膜透析（PD）过程中在腹膜腔中被激活，但其在长期PD相关的腹膜防御和损伤中的作用知之甚少。我们研究了葡萄糖和市售腹膜透析液对HPMCs中补体表达的影响，HPMCs是从同意接受择期腹部手术的患者的网膜组织中原代培养获得的。HPMCs中C3和C4 mRNA的组成型表达在暴露于75 mM葡萄糖后以时间依赖性方式上调。C3和C4蛋白在顶侧和基底侧两个方向分泌。超过100 mM的葡萄糖剂量显着下调C3和C4的表达，并刺激LDH释放剂量依赖性。使用等效剂量的甘露醇代替葡萄糖可减弱此类细胞毒性作用。用常规乳酸盐缓冲透析液处理引起HPMC中C3和C4表达下调，LDH释放增加。这些影响与溶液的葡萄糖强度相关，尽管用碳酸氢盐缓冲溶液替代，但仍持续存在，糖化白蛋白加重了这些影响，并通过在培养系统中补充10%胎牛血清部分消除了这些影响。我们的研究结果表明，PD施加的人工条件导致局部补体合成的改变，这对腹膜间皮在炎症和防御中的作用有影响。
Although complement is activated in the peritoneal cavity during chronic peritoneal dialysis (PD), little is known about its role in peritoneal defence and injury related to long-term PD. We examined the impact of glucose and commercial peritoneal dialysis solutions on complement expression in HPMCs obtained by primary culture from omental tissues of consented patients undergoing elective abdominal surgery. Constitutive expression of C3 and C4 mRNA in HPMCs was up-regulated upon exposure to 75 mM glucose in a time-dependent manner. C3 and C4 protein was secreted in both apical and basolateral directions. Glucose doses beyond 100 mM markedly down-regulated C3 and C4 expression, and stimulated LDH release dose-dependently. Such cytotoxic effects were attenuated using equivalent doses of mannitol instead of glucose. Treatment with conventional lactate-buffered dialysis solution gave rise to down-regulation of C3 and C4 expression, and heightened LDH release in HPMCs. These effects correlated with the glucose strength of the solution, persisted despite replacement with a bicarbonate-buffered solution, aggravated by glycated albumin, and were partially abrogated by supplementation with 10% fetal bovine serum in the culture system. Our findings suggest that the artificial conditions imposed by PD lead to alterations in local complement synthesis that have implications for the role of the peritoneal mesothelium in both inflammation and defence.