不同表面电荷的阳离子脂质体对人外周血单核细胞活化和细胞活性的影响

The Role of Surface Charge in Monocyte Activation and Cell Viability Induced by Cationic Liposomes

本文研究不同表面电荷的阳离子脂质体对人单核细胞活化和细胞活性的影响。将携带不同表面电荷的阳离子脂质体与人外周血单核细胞共育24h,然后采用流式细胞术和酶联免疫吸附法分别检测单核细胞表型、细胞活性以及细胞因子的分泌水平。实验结果显示,不同表面电荷的阳离子脂质体不同程度地诱导单核细胞活化,并表达共刺激分子CD86和分泌肿瘤坏死因子α。脂质体活化单核细胞的能力依赖于其表面电荷的强度,电荷过高或过低均可削弱其单核细胞活化作用。此外,阳离子脂质体对单核细胞具有一定的细胞毒性作用,并呈电荷依赖性。降低脂质体的表面电荷可显著降低其细胞毒性。因此,调整阳离子脂质体的表面电荷对于增强脂质体的免疫促进作用并减轻其副反应具有重要意义。

The present study investigated the effect of cationic liposomes with different surface charge on monocyte activation and viability.Liposomes were prepared by the thin-film hydration method,and the surface charge of cationic liposomes was adjusted by incorporating cationic liposome 1,2-dioleoyl-3-trimethylammonium-propane（DOTAP） with variable amount of neutral lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine（DOPC）.Monocytes were cultured with different cationic liposomes for 24 h,the expression of CD14 and CD86 on monocytes and cell viability were determined using flow cytometer.Cytokines in culture supenratants were measured using ELISA.The results showed that the cationic liposomes with the molar ratios of DOTAP to DOPC at 5：0,4：1,3：2 or 2：3 not only elevated CD86 on monocytes but also induced the production of tumor necrosis factor α（TNF α） suggesting cationic liposome induced monocyte activation.However,further increased proportion of DOPC significantly attenuated liposome-induced monocyte activation.On the other hand,DOTAP cationic liposome significantly reduced monocyte viability,indicating its potential toxic effect.Incorporating DOTAP with variable amount of DOPC significantly increased monocyte viability.Hence,an appropriate surface charge is crucial for enhancing the adjuvant effect of cationic liposome and reducing its potential toxic effect.