Synthesis and regulation of C1 inhibitor in human skin fibroblasts.
Synthesis and regulation of C1 inhibitor in human skin fibroblasts.
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DOI：
10.4049/jimmunol.142.6.2041
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发表时间：
1989-03
影响因子：
4.4
通讯作者：
Y. Katz;R. Strunk
中科院分区：
文献类型：
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作者：
Y. Katz;R. Strunk
已知补体激活经典途径的C1复合物的蛋白质C1 q、C1 r和C1 s在人皮肤成纤维细胞中合成。使用代谢标记与[35 S]蛋氨酸，免疫沉淀，和SDS-PAGE，我们证明，人皮肤成纤维细胞合成和分泌C1抑制剂的细胞裂解物中的表观分子量为78 kDa和102 kDa的细胞外介质中。该C1抑制剂具有结合活化的C1的能力。成纤维细胞合成的C1抑制剂比单核细胞合成的多30- 50倍。如前所述，成纤维细胞也合成C1 r和C1 s。IFN-γ、IFN-β 1和TNF对C1抑制剂C1 r和C1 s的合成具有显著但不同的影响。与IFN-γ，1000 U/ml，24小时的细胞孵育诱导C1抑制剂，C1 r，和C1 s的合成分别增加4.2-，1.9-和1.6-倍。IFN-β 1的作用与IFN-γ相似，但幅度较小。TNF，12.5 ng/ml，诱导C1抑制剂，C1 r和C1 s的合成增加1.5-，1.4-和2.6倍。IL-1、IFN-β 2（IL-6）和LPS不影响C1抑制剂、C1 r或C1 s的合成。成纤维细胞大量存在于大多数组织中。这些细胞合成C1抑制剂、C1 r和C1 s可以为身体组织中这些重要蛋白质提供来源。此外，成纤维细胞应该是一个很好的模型，在体外研究的遗传性疾病，涉及这些蛋白质的合成。
Proteins of the C1 complex, C1q, C1r, and C1s, of the classical pathway of complement activation are known to be synthesized in human skin fibroblasts. Using metabolic labeling with [35S]methionine, immunoprecipitation, and SDS-PAGE, we demonstrate that human skin fibroblasts synthesize and secrete C1 inhibitor with an apparent molecular mass of 78 kDa in the cell lysate and 102 kDa in the extracellular medium. This C1 inhibitor had the capacity to bind activated C1s. Fibroblasts synthesized 30- to 50-fold more C1 inhibitor than was synthesized in monocytes. As previously reported, fibroblasts also synthesized C1r and C1s. IFN-gamma, IFN-beta 1, and TNF had significant, but distinct, effects on synthesis of C1 inhibitor, C1r, and C1s. Incubation of the cells with IFN-gamma, 1000 U/ml, for 24 h induced increases in the synthesis of C1 inhibitor, C1r, and C1s by 4.2-, 1.9- and 1.6-fold, respectively. IFN-beta 1 had effects similar to IFN-gamma, although smaller in magnitude. TNF, 12.5 ng/ml, induced increases in the synthesis of C1 inhibitor, C1r, and C1s by 1.5-, 1.4- and 2.6-fold. IL-1, IFN-beta 2 (IL-6), and LPS did not affect synthesis of C1 inhibitor, C1r, or C1s. Fibroblasts are present in large amounts in most tissues. Synthesis of C1 inhibitor, C1r, and C1s by these cells could provide a source of these important proteins in body tissues. In addition, fibroblasts should be a good model for the in vitro study of genetic diseases involving the synthesis of these proteins.