Hymery N, Léon K, Carpentier F-G, Jung J-L, Parent-Massin D
Food Toxicology Laboratory, EA 3880, UFR Sciences et Techniques, 6 avenue Le Gorgeu-CS 93837-29238 Brest cedex 3, Brest University, France.
Toxicol In Vitro. 2009 Apr;23(3):509-19. doi: 10.1016/j.tiv.2009.01.003.
The aim of this work was to study the in vitro effect of T-2 toxin on human monocyte differentiation into macrophages and dendritic cells. Cytotoxicity of T-2 toxin on monocytes, on monocytes in differentiation process into macrophages or dendritic cells, and on immature dendritic cells and macrophages was evaluated to determine IC50. Monocytes are more sensitive to T-2 toxin than to differentiate cells. IC50 were equal to 0.11 nM for monocyte, to 45 and 30 nM for monocyte during differentiation process for 24 and 48 h of incubation, respectively, to 38 and 20 nM for immature dendritic cells after 24 and 48 h of incubation, and to 22 and 20 nM for macrophages after 24 and 48 h of incubation. T-2 toxin effects on monocyte differentiation process into macrophages have been explored: according to phenotypic expressions (CD71, CD14, CD11a, CD80, CD86, HLA-DR and CD64), endocytic capacity, phagocytosis, burst respiratory activity and TNF-alpha secretion. In the presence of 10 nM of T-2 toxin (no cytotoxic concentration), CD71 expression is downregulated compared to control. Endocytosis and phagocytosis capacities are less effective as burst respiratory activity and TNF-alpha secretion. Monocyte differentiation process into dendritic cells in the presence of 10 nM T-2 toxin is also markedly disturbed. Expression of CD1a (specific dendritic cells marker) is downregulated while that of CD14 (specific monocyte marker) is upregulated. CD11a, CD80, CD86, HLA-DR and CD64 expressions did not change. These results show that T-2 toxin disturbs human monocytes differentiation process into macrophages and dendritic cells. These results could significantly contribute to immunosuppressive properties of this alimentary toxin.
本研究旨在探讨T-2毒素对人单核细胞分化为巨噬细胞和树突状细胞的体外影响。评估T-2毒素对单核细胞、处于分化为巨噬细胞或树突状细胞过程中的单核细胞、未成熟树突状细胞和巨噬细胞的细胞毒性，以确定半数抑制浓度（IC50）。单核细胞对T-2毒素比分化细胞更敏感。单核细胞的IC50等于0.11 nM，在分化过程中培养24小时和48小时的单核细胞分别为45 nM和30 nM，培养24小时和48小时的未成熟树突状细胞分别为38 nM和20 nM，培养24小时和48小时的巨噬细胞分别为22 nM和20 nM。已探究T-2毒素对单核细胞分化为巨噬细胞过程的影响：根据表型表达（CD71、CD14、CD11a、CD80、CD86、HLA-DR和CD64）、内吞能力、吞噬作用、呼吸爆发活性和肿瘤坏死因子-α分泌进行评估。在存在10 nM T-2毒素（无细胞毒性浓度）的情况下，与对照组相比，CD71表达下调。内吞和吞噬能力不如呼吸爆发活性和肿瘤坏死因子-α分泌有效。在存在10 nM T-2毒素的情况下，单核细胞分化为树突状细胞的过程也受到明显干扰。CD1a（特异性树突状细胞标志物）的表达下调，而CD14（特异性单核细胞标志物）的表达上调。CD11a、CD80、CD86、HLA-DR和CD64的表达未改变。这些结果表明，T-2毒素扰乱人单核细胞分化为巨噬细胞和树突状细胞的过程。这些结果可能对这种食源性毒素的免疫抑制特性有显著贡献。
