为了探讨重金属砷、镉和铅对树突状细胞的毒性作用和功能影响,以骨髓源性树突状细胞(Bone marrow-derived dendritic cell,BMDC)为研究对象,采用 Alamar blue 法测定 BMDC 细胞的活性,采用流式细胞术检测BMDC细胞的凋亡、活化、吞噬以及抗原结合能力,并对细胞活性氧和丙二醛进行测定;采用荧光定量PCR检测BMDC细胞促炎/抗炎细胞因子的胞内表达水平。结果发现,3种重金属均可引起BMDC细胞活性降低(其中镉和铅可促进细胞凋亡)、导致细胞膜通透性改变并抑制细胞的活化;但3种重金属对BMDC细胞的功能影响存在差异,体现在砷可抑制BMDC细胞的吞噬功能,而铅和高浓度的锡则抑制BMDC细胞的抗原结合能力,同时促进促炎细胞因子的表达。上述结果表明,不同重金属对树突状细胞具有相似的细胞毒性,但对其功能的影响存在差异,其中,砷主要影响未成熟树突状细胞的吞噬功能,铅和镉则主要影响成熟树突状细胞的抗原结合功能。
Diverse effects of heavy metals on the functions of dendritic cells
In order to investigate the toxic effects and functional inhibition of typical heavy metals on dendritic cells,bone marrow-derived dendritic cells(BMDCs)were treated with arsenic(As),cadmium(Cd),or lead(Pb).BMDCs were stained with Alamar Blue to examine cell viability.Flow cytometry was employed to investigate the apoptosis,cell activation,phagocytosis,antigen binding capacity,and the levels of cellular reactive oxygen species and malondialdehyde for BMDCs.By using RT-qPCR,the expression levels of pro-and anti-inflammatory cytokines in BMDCs were also determined.The results demonstrated that all three heavy metals reduced BMDC activity,in which Cd and Pb promoted the apoptosis of BMDCs.Exposure to As,Cd or Pb altered cell membrane permeability and prevented the activation of BMDCs.However,As,Cd and Pb showed varied effects on BMDC functions,in which As prevented the phagocytosis capability while Pb and high-dosed Cd prevented the antigen-binding capacity of BMDCs.In conclusion,As,Cd and Pb exhibited comparable cytotoxic effects on dendritic cells,but varied impacts on the functions of dendritic cells.
heavy metalsdendritic cellscell activationantigen recognitionphagocytosis