Robey F A, Ohura K, Futaki S, Fujii N, Yajima H, Goldman N, Jones K D, Wahl S
J Biol Chem. 1987 May 25;262(15):7053-7.
We have studied the ability of human C-reactive protein to modulate the immune response in vitro. Whereas native C-reactive protein did not induce phagocytic leukocytes to chemotax or to produce superoxide, treatment of purified C-reactive protein with human neutrophil-derived acid proteases produced substances with potent effects on leukocyte function. Close examination of the primary structure of human C-reactive protein revealed three regions evenly distributed throughout the protein each of which contain peptide sequences closely resembling the amino acid sequence of the immunomodulator peptide tuftsin, Thr-Lys-Pro-Arg. We have synthesized the three peptides which include Thr-Lys-Pro-Leu ([Leu4]tuftsin), Gly-Lys-Pro-Arg ([Gly1]tuftsin), and Thr-Lys-Pro-Gln ([Gln4]tuftsin) and assayed them for biological activity. The three synthetic peptides were found to stimulate phagocytic leukocytes to chemotax, produce superoxide, and induce mononuclear cells to produce interleukin 1 in vitro at concentrations similar to those concentrations required for tuftsin to induce these phenomena. These results support a potentially important role for C-reactive protein as a possible immunomodulator during inflammation.
我们研究了人C反应蛋白在体外调节免疫反应的能力。天然C反应蛋白不会诱导吞噬性白细胞发生趋化作用或产生超氧化物，而用人中性粒细胞衍生的酸性蛋白酶处理纯化的C反应蛋白会产生对白细胞功能有强效作用的物质。对人C反应蛋白一级结构的仔细研究揭示，在整个蛋白质中均匀分布着三个区域，每个区域都含有与免疫调节肽促吞噬素（苏氨酸-赖氨酸-脯氨酸-精氨酸）的氨基酸序列极为相似的肽序列。我们合成了三种肽，分别是苏氨酸-赖氨酸-脯氨酸-亮氨酸（[亮氨酸4]促吞噬素）、甘氨酸-赖氨酸-脯氨酸-精氨酸（[甘氨酸1]促吞噬素）和苏氨酸-赖氨酸-脯氨酸-谷氨酰胺（[谷氨酰胺4]促吞噬素），并检测了它们的生物活性。结果发现，这三种合成肽在体外能刺激吞噬性白细胞发生趋化作用、产生超氧化物，并诱导单核细胞产生白细胞介素1，其所需浓度与促吞噬素诱导这些现象所需的浓度相似。这些结果支持了C反应蛋白在炎症过程中作为一种可能的免疫调节因子发挥潜在重要作用的观点。
