Moutabarrik A, Nakanishi I, Matsumoto M, Zaid D, Seya T
Department of Nephrology, Faculty of Medicine, Casablanca, Morocco.
Nephron. 1995;70(1):55-61. doi: 10.1159/000188544.
Complement proteins in serum are mainly synthesized by hepatocytes. Recently, many cell types have been reported to synthesize complement in various tissues. In this study, we report the synthesis and secretion of the third component of complement (C3) by cultured glomerular epithelial cells (GEC). Using reverse transcriptase polymerase reaction, we have found that GEC and whole kidney expressed the C3 mRNA for C3. By ELISA, we have found that C3 was secreted in culture supernatants harvested from cultured GEC. The secretion of C3 is regulated by proinflammatory cytokines (IL-1 beta, TNF-alpha and IL-6). IL-1 beta is shown to be the most potent stimulator of C3 secretion from GEC. The exact significance of C3 produced at glomerular site is not clear, but its upregulation by proinflammatory cytokines may suspect a role in local activation of complement which may lead to glomerular injury. We further studied the expression of C3 step regulatory proteins (membrane cofactor protein (MCP), decay-accelerating factor (DAF), CR-1 and CD59 (a terminal step regulatory protein) by cultured GEC. Treatment of GEC by proinflammatory cytokines IL-1 beta, TGF-beta, TNF-alpha and IL-6 did not modify the expression of MCP, DAF and CR-1 whereas an increase in the expression of CD59 could be observed after treatment with IL-1 beta and TGF-beta. These results indicate that the expression of these regulatory proteins is tissue specific and may be implicated in inflammatory processes.
血清中的补体蛋白主要由肝细胞合成。最近,有报道称多种细胞类型可在不同组织中合成补体。在本研究中,我们报告了培养的肾小球上皮细胞(GEC)可合成并分泌补体第三成分(C3)。通过逆转录聚合酶反应,我们发现GEC和整个肾脏均表达C3的C3 mRNA。通过酶联免疫吸附测定,我们发现从培养的GEC收获的培养上清液中分泌了C3。C3的分泌受促炎细胞因子(IL-1β、TNF-α和IL-6)调节。IL-1β被证明是GEC分泌C3的最有效刺激物。肾小球部位产生的C3的确切意义尚不清楚,但其被促炎细胞因子上调可能提示其在补体局部激活中起作用,这可能导致肾小球损伤。我们进一步研究了培养的GEC对C3级联调节蛋白(膜辅因子蛋白(MCP)、衰变加速因子(DAF)、CR-1和CD59(一种终末级联调节蛋白))的表达。用促炎细胞因子IL-1β、TGF-β、TNF-α和IL-6处理GEC并未改变MCP、DAF和CR-1的表达,而在用IL-1β和TGF-β处理后可观察到CD59表达增加。这些结果表明这些调节蛋白的表达具有组织特异性,可能与炎症过程有关。