EXPRESSION AND TISSUE LOCALIZATION OF DONOR-SPECIFIC COMPLEMENT C3 SYNTHESIZED IN HUMAN RENAL-ALLOGRAFTS
EXPRESSION AND TISSUE LOCALIZATION OF DONOR-SPECIFIC COMPLEMENT C3 SYNTHESIZED IN HUMAN RENAL-ALLOGRAFTS
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DOI：
10.1002/eji.1830250434
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发表时间：
1995-04-01
影响因子：
5.4
通讯作者：
SACKS, SH
中科院分区：
文献类型：
--
作者：
ANDREWS, PA;FINN, JE;SACKS, SH
最近的证据表明，补体的第三组分C3是在肾组织中合成的，C3合成增加发生在同种移植排斥反应和免疫复合体介导的肾炎中。然而，目前尚不清楚炎症浸润物中的固有肾细胞或移行细胞是C3的来源，可能来自受者骨髓。这是通过测定移植的人类肾脏产生的C3同种异型的mRNA和蛋白质来研究的。检查了20对供受者，其中9对在C3F/S基因座信息不匹配的C3等位基因。逆转录聚合酶链式反应(RT-PCR)和扩增难扩增突变系统分析显示，在这9例患者中，有6例在移植后61天出现了供体特异性mRNA的细胞内表达。套式聚合酶链式反应和扩增产物的大小排除了基因组DNA的污染。肾皮质冰冻切片的同种异型特异性染色显示，所有活检组织的肾小球和肾小管均有供体来源的C3蛋白，主要分布在肾小管。这些结果表明，补体的至少部分促炎作用来自供体C3的内在组织合成，这可能代表了一种以前未被认识的组织损伤来源。供体同种异型C3局部合成的发生可能与C3同种异型有关，也可能与抑制肾内补体介导的损伤有关。
Recent evidence suggests that the third component of complement, C3, is synthesized in renal tissue, and that increased C3 synthesis occurs in allograft rejection and immune complex-mediated nephritis. However, it is unclear whether intrinsic renal cells or migratory cells in the inflammatory infiltrate, possibly of recipient bone marrow origin, are the source of the C3 detected. This was investigated by determining the C3 allotypes of mRNA and protein produced by transplanted human kidney. Twenty donor-recipient pairs were examined, of which nine pairs had C3 allotypes that were informatively mismatched at the C3 F/S locus. Reverse transcriptase polymerase chain reaction (RT-PCR) followed by amplification refractory mutation system analysis showed intracellular donor-specific mRNA expression in six of these nine cases, at up to 61 days post-transplantation. Nested PCR reactions and the size of PCR products excluded contamination by genomic DNA. Allotype-specific staining of frozen sections of renal cortex demonstrated donor-derived C3 protein in both glomeruli and tubules of all biopsies examined, in a predominantly tubular distribution. These results imply that at least some of the pro-inflammatory effects of complement arise from intrinsic tissue synthesis of donor C3, and that this may represent a previously unrecognized source of tissue injury. The occurrence of local synthesis of C3 of donor allotype may have functional implications related to C3 allotype, and may also be relevant to strategies to inhibit intrarenal complement-mediated injury.