Shi Jun, Ikeda Kazuma, Fujii Nobuharu, Kondo Eisei, Shinagawa Katsuji, Ishimaru Fumihiko, Kaneda Kinuyo, Tanimoto Mitsune, Li Xiao, Pu Quan
Hematology Department, Sixth Hospital of Shanghai Jiaotong University, Shanghai 200233, China.
Cancer Sci. 2005 Feb;96(2):127-33. doi: 10.1111/j.1349-7006.2005.00017.x.
Apart from their role as antigen presenting cells, human peripheral blood monocyte and CD34+ cell-derived dendritic cells (DC), have been demonstrated to exert cytotoxicity against some tumor cells, and their tumoricidal activity can be enhanced by some stimili. However, there have been no reports concerning the tumoricidal activity of human cord blood dendritic cells (CBDC). In this article, we report that human cord blood monocyte-derived DC acquire the ability to kill hematological tumor cells, after activation with lipopolysaccharide (LPS) or gamma-interferon (IFN-gamma), associated with the enhanced TNF-alpha-related apoptosis-inducing ligand (TRAIL) expression in CBDC cytoplasm. The CD14-positive cells collected from cord blood were induced to CBDC in vitro. After activation with IFN-gamma for 12 h, CBDC exhibited cytotoxicity against HL60 and Jurkat cells, while activation with LPS induced cytotoxicity against Daudi and Jurkat cells. However, both LPS- and IFN-gamma-stimulated CBDC showed no cytotoxic activity against normal CD14-negative cord blood mononuclear cells. The formation of umbilical cord hematopoietic progenitor colonies, identified as burst-forming unit-erythroid and colony-forming unit granulocyte-macrophage, was not inhibited by stimulated or unstimulated CBDC. IFN-gamma or LPS stimulation enhanced intracellular but not cellular surface TRAIL, and neither intracellular nor cellular surface tumor necrosing factor-alpha and Fas Ligand as analyzed by flow cytometry. Our results show that activated CBDC can serve as cytotoxic cells against hematological tumor cells without damaging the normal hematopoietic progenitor cells.
除了作为抗原呈递细胞的作用外，人外周血单核细胞和CD34+细胞来源的树突状细胞（DC）已被证明对某些肿瘤细胞具有细胞毒性，并且它们的杀肿瘤活性可被某些刺激物增强。然而，关于人脐血树突状细胞（CBDC）的杀肿瘤活性尚无报道。在本文中，我们报告人脐血单核细胞来源的DC在用脂多糖（LPS）或γ干扰素（IFN-γ）激活后获得了杀死血液肿瘤细胞的能力，这与CBDC细胞质中TNF-α相关凋亡诱导配体（TRAIL）表达增强有关。从脐血中收集的CD14阳性细胞在体外被诱导为CBDC。用IFN-γ激活12小时后，CBDC对HL60和Jurkat细胞表现出细胞毒性，而用LPS激活则诱导对Daudi和Jurkat细胞的细胞毒性。然而，LPS和IFN-γ刺激的CBDC对正常CD14阴性脐血单核细胞均无细胞毒性活性。被鉴定为红系爆式集落形成单位和粒-巨噬系集落形成单位的脐血造血祖细胞集落的形成不受刺激或未刺激的CBDC抑制。通过流式细胞术分析，IFN-γ或LPS刺激增强了细胞内而非细胞表面的TRAIL，并且细胞内和细胞表面的肿瘤坏死因子-α和Fas配体均未增强。我们的结果表明，活化的CBDC可作为针对血液肿瘤细胞的细胞毒性细胞，而不会损害正常造血祖细胞。
