Rothman B L, Contrino J, Merrow M, Despins A, Kennedy T, Kreutzer D L
Department of Pathology, University of Connecticut Health Center, Farmington.
Immunopharmacol Immunotoxicol. 1994 Nov;16(4):525-51. doi: 10.3109/08923979409019738.
Although investigations to date have demonstrated the ability of the monocyte/macrophage to synthesize complement components, only a limited number of studies on complement synthesis by nonhepatic tissue cells have been reported. To begin to fill this gap in our knowledge we have recently evaluated the ability of lung tissue cells to synthesize and secrete various complement components in vitro. Using 35S-methionine incorporation and immunoprecipitation techniques we have previously demonstrated the ability human lung type II pneumocytes (A549) and human lung fibroblasts (WI-38), to synthesize and secrete a variety of both early and terminal complement components, as well as several regulatory proteins including Clr, Cls, C4, C3, C5, C6, C7, C8, C9, Factor B, Factor H, Factor I and Cls inactivator. Our present studies demonstrate the capability of silica to regulate complement component production by A549 cells, but not complement component production by WI-38 cells. Specifically, using sensitive ELISAs we demonstrated that a non-toxic dose of silica had the capability to suppress the production of both C3 and C5 by A549 pneumocytes by 40-50 percent, but had no effect on C3 or C5 synthesis by WI-38 fibroblasts. Additionally, using 35S-methionine incorporation and TCA precipitation techniques, we demonstrated that suppression of C3 and C5 production by silica treated A549 pneumocytes was not a result of suppression of total protein synthesis. These studies demonstrate that silica, which has been implicated in pulmonary diseases, has the capability to regulate local complement production by lung tissue cells in vitro. In vivo, this suppression of complement production by the type II pneumocytes could alter the local tissue reservoir of complement components during infection and pulmonary injury, thus resulting in depressed pulmonary host defense.
尽管迄今为止的研究已证明单核细胞/巨噬细胞具有合成补体成分的能力，但关于非肝组织细胞补体合成的研究报道却为数不多。为了填补这一知识空白，我们最近评估了肺组织细胞在体外合成和分泌各种补体成分的能力。我们先前利用35S-甲硫氨酸掺入和免疫沉淀技术，证明了人肺II型肺泡上皮细胞（A549）和人肺成纤维细胞（WI-38）能够合成和分泌多种早期及终末补体成分，以及几种调节蛋白，包括Clr、Cls、C4、C3、C5、C6、C7、C8、C9、B因子、H因子、I因子和Cls灭活剂。我们目前的研究表明，二氧化硅能够调节A549细胞的补体成分生成，但对WI-38细胞的补体成分生成没有影响。具体而言，我们使用灵敏的酶联免疫吸附测定法（ELISA）证明，无毒剂量的二氧化硅能够使A549肺泡上皮细胞的C3和C5生成量分别减少40%至50%，但对WI-38成纤维细胞的C3或C5合成没有影响。此外，利用35S-甲硫氨酸掺入和三氯乙酸沉淀技术，我们证明二氧化硅处理的A549肺泡上皮细胞中C3和C5生成的抑制并非总蛋白合成受抑制的结果。这些研究表明，与肺部疾病有关的二氧化硅能够在体外调节肺组织细胞的局部补体生成。在体内，II型肺泡上皮细胞补体生成的这种抑制可能会在感染和肺损伤期间改变补体成分的局部组织储备，从而导致肺部宿主防御功能下降。
