Heidenreich Silke, Zu Eulenburg Christine, Hildebrandt York, Stübig Thomas, Sierich Heidi, Badbaran Anita, Eiermann Thomas H, Binder Thomas M C, Kröger Nicolaus
Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Clin Dev Immunol. 2012;2012:652130. doi: 10.1155/2012/652130. Epub 2012 Jul 10.
The role of different receptors in natural-killer- (NK-) cell-mediated cytotoxicity against multiple myeloma (MM) cells is unknown. We investigated if an enhancement of NK-cell-mediated cytotoxicity against MM could be reached by blocking of the inhibitory leukocyte immunoglobulin-like receptor 1 (LIR-1). Our investigations revealed high levels of LIR-1 expression not only on the NK cell line NK-92, but also on myeloma cells (MOLP-8, RPMI8226) as well as on a lymphoblastoid cell line (LBCL; IM-9). Subsequent cytotoxicity assays were designed to show the isolated effects of LIR-1 blocking on either the effector or the tumor side to rule out receptor-receptor interactions. Although NK-92 was shown to be capable of myeloma cell lysis, inhibition of LIR-1 on NK-92 did not enhance cytotoxicity. Targeting the receptor on MM and LBCL did not also alter NK-92-mediated lysis. We come to the conclusion that LIR-1 alone does not directly influence NK-cell-mediated cytotoxicity against myeloma. To our knowledge, this work provides the first investigation of the inhibitory capability of LIR-1 in NK-92-mediated cytotoxicity against MM and the first functional evaluation of LIR-1 on MM and LBCL.
不同受体在自然杀伤细胞（NK细胞）介导的针对多发性骨髓瘤（MM）细胞的细胞毒性中所起的作用尚不清楚。我们研究了通过阻断抑制性白细胞免疫球蛋白样受体1（LIR-1）是否能够增强NK细胞介导的针对MM的细胞毒性。我们的研究表明，LIR-1不仅在NK细胞系NK-92上高表达，在骨髓瘤细胞（MOLP-8、RPMI8226）以及淋巴母细胞系（LBCL；IM-9）上也高表达。随后设计细胞毒性试验以显示LIR-1阻断在效应细胞或肿瘤细胞一侧的单独作用，从而排除受体-受体相互作用。尽管已证明NK-92能够裂解骨髓瘤细胞，但抑制NK-92上的LIR-1并未增强细胞毒性。靶向MM和LBCL上的该受体也未改变NK-92介导的裂解作用。我们得出结论，单独的LIR-1并不直接影响NK细胞介导的针对骨髓瘤的细胞毒性。据我们所知，这项工作首次研究了LIR-1在NK-92介导的针对MM的细胞毒性中的抑制能力，并首次对LIR-1在MM和LBCL上进行了功能评估。
