Brooimans R A, Stegmann A P, van Dorp W T, van der Ark A A, van der Woude F J, van Es L A, Daha M R
Department of Nephrology, University Hospital, Leiden, The Netherlands.
J Clin Invest. 1991 Aug;88(2):379-84. doi: 10.1172/JCI115314.
Previous reports have suggested the production of complement components C4, C2, and factor B by renal tissue. However, the cells involved in production of complement have not been identified. In this study metabolic labeling experiments demonstrated that human proximal tubular epithelial cells (PTEC) synthesize a 180-kD precursor of C3 that is secreted after proteolytic cleavage into a disulphide linked two-chain molecule as found in plasma. C3 present in culture supernatants of PTEC was functionally active, however, during the culture period there was a partial inactivation of the C3 molecule as assessed by hemolytic titration. Recombinant IL-2 enhances the rate of C3 synthesis in a dose-dependent manner reaching maximal stimulation at doses of 200-400 U/ml IL-2. Northern blot analysis demonstrated a 5.2-kb C3 mRNA species present in PTEC that was increased within 24 h of IL-2 treatment. IL-2-induced enhancement of C3 production by PTEC could be neutralized with specific antibodies to IL-2. This study demonstrates that C3 synthesis in PTEC is upregulated by IL-2, the major cytokine produced by activated T cells.
先前的报告提示肾组织可产生补体成分C4、C2和B因子。然而，参与补体产生的细胞尚未明确。在本研究中，代谢标记实验表明，人近端肾小管上皮细胞（PTEC）合成一种180-kD的C3前体，该前体经蛋白水解裂解后分泌为血浆中所见的二硫键连接的双链分子。PTEC培养上清液中的C3具有功能活性，然而，在培养期间，通过溶血滴定评估发现C3分子存在部分失活。重组白细胞介素-2（IL-2）以剂量依赖方式提高C3合成速率，在200-400 U/ml IL-2剂量时达到最大刺激。Northern印迹分析显示PTEC中存在一种5.2-kb的C3 mRNA，其在IL-2处理后24小时内增加。PTEC中IL-2诱导的C3产生增强可被抗IL-2特异性抗体中和。本研究表明，PTEC中的C3合成受IL-2上调，IL-2是活化T细胞产生的主要细胞因子。
