Rothman B L, Despins A W, Kreutzer D L
Department of Pathology, University of Connecticut Health Center, Farmington 06032.
J Immunol. 1990 Jul 15;145(2):592-8.
A growing body of literature suggests that a variety of cell products (e.g., cytokines, C components, etc.) likely play an important role during inflammation and host defense by locally regulating the diverse functions of recruited (i.e., immunologic cells) as well as tissue cells. Previously, a number of investigations have demonstrated the ability of immunologic cells to produce C components in vitro, and further studies have identified a variety of cytokines that can regulate C component production by these cells. Recently, we have demonstrated the ability of lung tissue cells, including epithelial cells and fibroblasts, to synthesize and secrete numerous C components and complement regulatory proteins in vitro. Additionally, we have demonstrated that C component production can be modulated by a variety of factors including endotoxin and serum. In our studies we investigated the effects of specific cytokines, i.e., IL and IFN, on the production of the third (C3) and fifth (C5) C components by the continuous cell line of human type II pneumocytes (A549). Specifically, using sensitive ELISA we demonstrated that A549 pneumocytes exposed to IL-1 alpha, IL-1 beta, or IL-2 induced a dose-dependent, more than twofold, increase in C3 production and a 50% decrease in C5 production when compared to control (untreated) A549 cells. Interestingly, IFN-alpha significantly decreased both C3 and C5 production, i.e., 38 and 71%, respectively, in a dose-dependent manner. IFN-gamma had no effect on C3 production, but significantly decreased C5 production by A549 pneumocytes by 84%. These data not only demonstrate that cytokines have the capability to modulate C3 and C5 production by human type II pneumocytes in vitro, but that C3 and C5 production by these cells can be regulated independently by different cytokines. In vivo, cytokine modulation of C component production by local tissue cells likely plays an important role in the regulation of inflammation and host defense within the lung.
越来越多的文献表明，多种细胞产物（如细胞因子、补体成分等）可能通过局部调节募集细胞（即免疫细胞）以及组织细胞的多种功能，在炎症和宿主防御过程中发挥重要作用。此前，多项研究已证明免疫细胞在体外产生补体成分的能力，进一步的研究还鉴定出多种可调节这些细胞补体成分产生的细胞因子。最近，我们已证明肺组织细胞，包括上皮细胞和成纤维细胞，在体外能够合成和分泌多种补体成分及补体调节蛋白。此外，我们还证明补体成分的产生可受到多种因素的调节，包括内毒素和血清。在我们的研究中，我们调查了特定细胞因子，即白细胞介素（IL）和干扰素（IFN），对人II型肺上皮细胞（A549）连续细胞系产生第三补体成分（C3）和第五补体成分（C5）的影响。具体而言，使用灵敏的酶联免疫吸附测定法（ELISA），我们证明与对照（未处理）的A549细胞相比，暴露于白细胞介素-1α、白细胞介素-1β或白细胞介素-2的A549肺上皮细胞可诱导C3产生呈剂量依赖性增加两倍以上，而C5产生减少50%。有趣的是，干扰素-α以剂量依赖性方式显著降低C3和C5的产生，分别降低38%和71%。干扰素-γ对C3产生没有影响，但显著降低A549肺上皮细胞的C5产生达84%。这些数据不仅证明细胞因子在体外有能力调节人II型肺上皮细胞的C3和C5产生，而且这些细胞的C3和C5产生可由不同细胞因子独立调节。在体内，局部组织细胞对补体成分产生的细胞因子调节可能在肺内炎症和宿主防御的调节中起重要作用。
