Brooimans R A, van der Ark A A, Buurman W A, van Es L A, Daha M R
Department of Nephrology, University Hospital, Leiden, The Netherlands.
J Immunol. 1990 May 15;144(10):3835-40.
Human umbilical vein endothelial cells (HUVEC) synthesize and secrete C component factors H and C3. Addition of T cell growth factor to HUVEC enhanced factor H production, and caused a profound increase in C3 production. In the present study, investigations were initiated to characterize the effects of purified rIL-1 and rIFN-gamma on the production of factor H and C3 at the protein and mRNA level. IFN-gamma enhanced factor H production in a dose-dependent fashion and a two-fold increase was observed with an optimal dose of 200 U/ml, whereas IFN-gamma had no effect on C3 production. IL-1 inhibited factor H secretion, but the production of C3 was increased 10-fold at an optimal dose of 500 pg/ml of IL-1. Kinetic experiments demonstrated that addition of IL-1 to HUVEC resulted in an induction of C3 production after more than 24 h, whereas IFN-gamma already had a significant effect on factor H production after 8 h of culture. IL-1 in combination with IFN-gamma had a synergistic effect on C3 production. The effects of IL-1 and IFN-gamma on factor H and C3 production by HUVEC could be blocked by using neutralizing amounts of antibodies specific for these cytokines. Northern blot analysis showed that factor H mRNA expression was enhanced in IFN-gamma-treated HUVEC and C3 mRNA was induced in IL-1-treated HUVEC, indicating that the observed increase of factor H and C3 probably is controlled by enhancement of transcription or stability of the transcript.
人脐静脉内皮细胞（HUVEC）合成并分泌补体成分因子H和C3。向HUVEC中添加T细胞生长因子可增强因子H的产生，并导致C3产生显著增加。在本研究中，开始进行调查以在蛋白质和mRNA水平上表征纯化的重组白细胞介素-1（rIL-1）和重组干扰素-γ（rIFN-γ）对因子H和C3产生的影响。干扰素-γ以剂量依赖性方式增强因子H的产生，在最佳剂量200 U/ml时观察到增加了两倍，而干扰素-γ对C3产生没有影响。白细胞介素-1抑制因子H的分泌，但在最佳剂量500 pg/ml的白细胞介素-1时C3的产生增加了10倍。动力学实验表明，向HUVEC中添加白细胞介素-1在超过24小时后导致C3产生的诱导，而干扰素-γ在培养8小时后已经对因子H的产生有显著影响。白细胞介素-1与干扰素-γ联合对C3产生有协同作用。使用针对这些细胞因子的中和量抗体可阻断白细胞介素-1和干扰素-γ对HUVEC产生因子H和C3的影响。Northern印迹分析表明，在干扰素-γ处理的HUVEC中因子H mRNA表达增强，在白细胞介素-1处理的HUVEC中C3 mRNA被诱导，表明观察到的因子H和C3的增加可能是由转录增强或转录本稳定性控制的。
