肺癌细胞裂解物对树突状细胞的免疫抑制作用

目的:研究Lewis肺癌细胞裂解物对小鼠树突状细胞(DC)的免疫抑制作用。方法:反复冻融法制备Lewis肺癌细胞裂解物,骨髓冲洗提取C57/BL6小鼠DC,GM-CSF、IL-4体外诱导培养DC,ELISA检测肿瘤细胞裂解物(TCL)中透明质酸(HA)含量,ELISA检测DC培养上清液中IL-12和IL-10水平。结果:经检测,Lewis肺癌细胞TCL中含有HA,其含量为42 mg/ml。将这种TCL作用于C57/BL6小鼠DC,同对照组相比,DC的IL-12分泌水平显著下降(P<0.01),而IL-10的分泌水平显著提高(P<0.01),这符合免疫耐受DC细胞因子分泌特点。在用Pep-1抗体封闭DC表面的HA受体CD44后,DC的IL-12、IL-10分泌水平则恢复至同对照组相同的水平(P>0.05)。结论:Lewis肺癌细胞裂解物中含有HA。通过这种物质,肺癌细胞裂解物可以诱生鼠源免疫耐受性DC,从而抑制DC的免疫活性。

Immunosuppressive effect of lung cancer cell lysates on the dendritic cells

Objective: To investigate the immunosuppressive effect of the lysates from Lewis lung cancer cells on mouse dendritic cells( DC). Methods:DCs were initially obtained from the C57 /BL6 mouse marrow. The lysates of Lewis lung cancer cells were prepared with repeated freezing-thawing technique,and in vitro cultured in granulocyte-macrophage colony-stimulating factor( GM-CSF) and interleukin-4( IL-4). ELISA was used to detect the concentration of hyaluronan( HA) in the tumor cell lysates( TCL) as well as the level of IL-12 and IL-10 in the culture supernatant of DCs. Results: HA was detected in the TCL of Lewis lung cancer cells,and its concentration reached 42 mg /ml. Once the TCL was delivered into the DCs of C57 /BL6 mice,whose IL-12 level in DCs was significantly decreased,whereas the IL-10 level was markedly increased as compared with the controls( P < 0. 01). These changes were complying with the immunological tolerance properties of DCs. However,IL-12 and IL-10 levels were restored equivalently to those of the control group after inhibition of the surface HA receptor CD44 in DCs using Pep-1 antibody( P > 0. 05). Conclusion: TCL of Lewis lung cancer contains a HA that is capable of inducing the immunogenic DC in mouse to eventually inhibit the immunocompetence of DCs.