Bjørge L, Jensen T S, Matre R
Department of Microbiology and Immunology, Gade Institute, University of Bergen, Norway.
Cancer Immunol Immunother. 1996 Mar;42(3):185-92. doi: 10.1007/s002620050269.
To avoid destruction by complement, normal and malignant cells express membrane glycoproteins that restrict complement activity. These include decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and protectin (CD59), which are all expressed on colonic adenocarcinoma cells in situ. In this study we have characterised the C3/C5 convertase regulators DAF and MCP on the human colonic adenocarcinoma cell line HT29. DAF was found to be a glycosyl-phosphatidylinositol-anchored 70-kDa glycoprotein. Blocking experiments with F(ab')2 fragments of the anti-DAF monoclonal antibody BRIC 216 showed that DAF modulates the degree of C3 deposition and mediates resistance to complement-mediated killing of the cells. The expression and function of DAF were enhanced by tumour necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta). Cells incubated with interferon gamma (IFN gamma) did not alter their DAF expression. Two MCP forms were expressed, with molecular masses of approximately 58 kDa and 68 kDa, the lower form predominating. MCP expression was up-regulated by IL-1 beta, but not by TNF alpha or INF gamma. Expression of DAF and MCP promotes resistance of colonic adenocarcinoma cells to complement-mediated damage, and represents a possible mechanism of tumour escape.
为避免被补体破坏，正常细胞和恶性细胞会表达限制补体活性的膜糖蛋白。这些蛋白包括衰变加速因子（DAF，CD55）、膜辅因子蛋白（MCP，CD46）和保护素（CD59），它们均原位表达于结肠腺癌细胞上。在本研究中，我们对人结肠腺癌细胞系HT29上的C3/C5转化酶调节因子DAF和MCP进行了特性分析。发现DAF是一种糖基磷脂酰肌醇锚定的70 kDa糖蛋白。用抗DAF单克隆抗体BRIC 216的F(ab')2片段进行的阻断实验表明，DAF可调节C3沉积程度，并介导细胞对补体介导杀伤的抗性。肿瘤坏死因子α（TNFα）和白细胞介素-1β（IL-1β）可增强DAF的表达和功能。用干扰素γ（IFNγ）孵育的细胞其DAF表达未改变。表达了两种MCP形式，分子量分别约为58 kDa和68 kDa，以较低分子量形式为主。IL-1β可上调MCP表达，但TNFα或INFγ则无此作用。DAF和MCP的表达促进结肠腺癌细胞对补体介导损伤的抗性，这代表了一种可能的肿瘤逃逸机制。
