Okamoto M, Inaba T, Yamada N, Uchida R, Fuchida S-I, Okano A, Shimazaki C, Taniwaki M
Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Cytotherapy. 2006;8(5):509-16. doi: 10.1080/14653240600957586.
The molecular mechanism of natural killer (NK) cell cytotoxicity to myeloma cells remains unclear. We investigated whether MHC class I-related chain (MIC), a ligand of NKG2D that is an activating NK cell receptor, is involved in the cytotoxicity of NK cells toward myeloma cells, and examined the effects of various drugs on the cytotoxicity.
Two human myeloma cell lines and fresh myeloma cells from 10 patients were used. MIC expression was examined by flow cytometry and reverse transcription (RT)-PCR. NK cell cytotoxicity was examined using a 51Cr-release assay. The effects of various drugs, including thalidomide, all-trans retinoic acid, dexamethasone, IFN-alpha and incadronate, on the MIC expression and NK cell cytotoxicity were examined.
MIC was highly expressed on the human myeloma cell lines U266 and RPMI-8226 and in myeloma cells of one of 10 patients examined. MIC expression on these cells was not changed by various drugs except IFN-alpha, by which MIC expression was down-regulated. Although MIC and HLA class I molecules were similarly expressed at high levels on both cell lines, U266 was sensitive to NK cells whereas RPMI-8226 was not. Furthermore, cytolysis by NK cells was not inhibited by the addition of anti-MIC Ab or decreased expression of MIC caused by IFN-alpha.
MIC plays a role in the cytolysis by NK cells in multiple myeloma.
自然杀伤（NK）细胞对骨髓瘤细胞的细胞毒性分子机制仍不清楚。我们研究了作为激活型NK细胞受体NKG2D配体的MHC I类相关链（MIC）是否参与NK细胞对骨髓瘤细胞的细胞毒性，并检测了各种药物对该细胞毒性的影响。
使用两个人骨髓瘤细胞系和10例患者的新鲜骨髓瘤细胞。通过流式细胞术和逆转录（RT）-PCR检测MIC表达。使用51Cr释放试验检测NK细胞的细胞毒性。检测了包括沙利度胺、全反式维甲酸、地塞米松、干扰素-α和英卡膦酸盐在内的各种药物对MIC表达和NK细胞细胞毒性的影响。
MIC在人骨髓瘤细胞系U266和RPMI-8226以及所检测的10例患者中的1例的骨髓瘤细胞上高表达。除干扰素-α可下调MIC表达外，各种药物均未改变这些细胞上的MIC表达。尽管MIC和HLA I类分子在两种细胞系上均以高水平类似表达，但U266对NK细胞敏感，而RPMI-8226则不敏感。此外，添加抗MIC抗体或干扰素-α导致的MIC表达降低均未抑制NK细胞的细胞溶解作用。
MIC在多发性骨髓瘤中NK细胞的细胞溶解作用中发挥作用。
