Expression of rat complement control protein Crry on tumor cells inhibits rat natural killer cell-mediated cytotoxicity
Expression of rat complement control protein Crry on tumor cells inhibits rat natural killer cell-mediated cytotoxicity
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DOI：
10.1182/blood.v100.9.3304
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发表时间：
2002-11-01
期刊：
影响因子：
20.3
通讯作者：
Tomlinson, S
中科院分区：
文献类型：
--
作者：
Caragine, TA;Imai, M;Tomlinson, S
Crry是一种啮齿类动物补体激活的膜结合抑制剂，是人补体抑制剂衰变加速因子和膜辅因子蛋白的结构和功能类似物。我们先前发现，大鼠Crry在人肿瘤细胞系上的表达增强了裸大鼠的致瘤性。在本研究中，我们研究了在肿瘤细胞上表达的大鼠Crry对大鼠细胞介导的细胞毒性和抗体依赖性细胞介导的细胞毒性（ADCC）的影响。大鼠Crry在不同人肿瘤细胞系表面的表达可抑制大鼠自然杀伤（NK）细胞介导的ADCC。已知C3调理作用增强NK细胞介导的细胞溶解，并且Crry介导的NK细胞溶解抑制的潜在机制是通过Crry调节靶细胞上的C3沉积。然而，在不存在外源性补体的情况下，用Crry转染肿瘤细胞系增强了它们对NK细胞介导的裂解的抗性。表达Crry的肿瘤细胞对NK细胞介导的ADCC的抗性可通过抗Crry F（ab）治疗逆转（2）。此外，抗Crry F（ab）2增强了13762大鼠乳腺癌细胞（内源性表达Crry）对在不存在添加补体的情况下由同种异体大鼠NK细胞介导的ADCC的易感性。我们没有发现证据表明大鼠NK细胞是在体外细胞溶解试验中靶细胞沉积的补体来源。这些数据表明，大鼠Crry在肿瘤免疫监视中的新功能可能与补体抑制无关。(C)2002年，美国血液学会。
Crry is a rodent membrane-bound inhibitor of complement activation and is a structural and functional analog of the human complement inhibitors decay-accelerating factor and membrane cofactor protein. We found previously that expression of rat Crry on a human tumor cell line enhances tumorigenicity in nude rats. In this study, we investigated the effect that rat Crry expressed on tumor cells has on rat cell-mediated cytotoxicity and anti body-dependent cell-mediated cytotoxicity (ADCC). The expression of rat Crry on the surface of different human tumor cell lines inhibited ADCC mediated by rat natural killer (NK) cells. C3 opsonization is known to enhance NK cell-mediated cytolysis, and a potential mechanism for Crry-mediated inhibition of NK cell lysis is through Crry modulation of C3 deposition on target cells. However, the transfection of tumor cell lines with Crry enhanced their resistance to NK cell-mediated lysis in the absence of exogenous complement. The resistance of Crry-expressing tumor cells to NK cell-mediated ADCC could be reversed by treatment with anti-Crry F(ab)(2). In addition, anti-Crry F(ab)2 enhanced the susceptibility of 13762 rat mammary adenocarcinoma cells (that endogenously express Crry) to ADCC mediated by allogeneic rat NK cells in the absence of added complement. We found no evidence that rat NK cells were a source of complement for target cell deposition during the in vitro cytolysis assay. These data suggest a novel function for rat Crry in tumor immune surveillance that may be unrelated to complement inhibition. (C) 2002 by The American Society of Hematology.