Goslings W R, Blom D J, de Waard-Siebinga I, van Beelen E, Claas F H, Jager M J, Gorter A
Department of Ophthalmology, Leiden University Hospital, Netherlands.
Invest Ophthalmol Vis Sci. 1996 Aug;37(9):1884-91.
To identify the presence of membrane-bound regulators of complement activation (m-RCA) on uveal melanomas and uveal melanoma cell lines and to examine their role in the inhibition of complement-mediated lysis in vitro.
Immunohistochemistry and flow cytometric analysis with monoclonal antibodies directed against m-RCA CD46, CD55, and CD59 were applied to tissue sections of 10 uveal melanomas, three primary uveal melanoma cell lines, and one uveal melanoma metastatic cell line. A microcytotoxicity test was used for measuring antibody-dependent complement-mediated lysis.
The tissue sections and all four uveal melanoma cell lines expressed CD46, CD55, and CD59. Complement-mediated lysis in the presence of human complement was increased after partial removal of the m-RCA CD55 and CD59 with phosphatidylinositol-specific phospholipase C from the uveal melanoma cell line 92-1.
These results demonstrate that CD46, CD55, and CD59 are expressed in uveal melanomas and that CD55 or CD59, or both, plays a role in resistance to complement-mediated cytotoxicity. The finding that m-RCA are expressed in uveal melanomas may have implications for the effectiveness of the anti-tumor response and in the therapeutic application of monoclonal antibodies directed against tumor-associated antigens.
鉴定葡萄膜黑色素瘤及葡萄膜黑色素瘤细胞系中补体激活的膜结合调节因子(m-RCA)的存在,并检测它们在体外抑制补体介导的细胞溶解中的作用。
应用针对m-RCA CD46、CD55和CD59的单克隆抗体进行免疫组织化学和流式细胞术分析,检测10例葡萄膜黑色素瘤组织切片、3个原发性葡萄膜黑色素瘤细胞系和1个葡萄膜黑色素瘤转移细胞系。采用微细胞毒性试验检测抗体依赖性补体介导的细胞溶解。
组织切片及所有4个葡萄膜黑色素瘤细胞系均表达CD46、CD55和CD59。用磷脂酰肌醇特异性磷脂酶C从葡萄膜黑色素瘤细胞系92-1中部分去除m-RCA CD55和CD59后,人补体存在时补体介导的细胞溶解增加。
这些结果表明,CD46、CD55和CD59在葡萄膜黑色素瘤中表达,且CD55或CD59,或两者均在抵抗补体介导的细胞毒性中发挥作用。葡萄膜黑色素瘤中表达m-RCA这一发现可能对抗肿瘤反应的有效性以及针对肿瘤相关抗原的单克隆抗体的治疗应用具有重要意义。