不同水合粒径的磷酸镧微粒对巨噬细胞IL-1β分泌水平的影响以及与其入胞途径的相关性  

Effect of Lanthanum Phosphate Particles with Various Hydrodynamic Diameters on IL-1β Secretion of Macrophages and Relationship with Transport Processes

作　　者：孙冀芳 刘会雪[1] 杨晓达[1] 杨晓改[1] 王夔[1] Sun Jifang;Liu Huixue;Yang Xiaoda;Yang Xiaogai;Wang Kui(School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)

机构地区：[1]北京大学药学院,北京100191

出　　处：《中国稀土学报》2023年第3期631-640,I0006,共11页Journal of the Chinese Society of Rare Earths

基　　金：国家自然科学基金项目(21277006,22177007)资助。

摘　　要：基于稀土的应用现状,本研究以人源THP-1巨噬细胞(THP-M)为研究模型,选取了具不同水合粒径大小的LaPO_4微粒,研究了它们刺激THP-M IL-1β分泌水平的差异性以及入胞途径与IL-1β分泌水平的相关性。研究表明,LaCl_3在含不同血清的培养基中可形成水合粒径大小不同的磷酸镧微粒;水合粒径越大,刺激THP-M分泌IL-1β的水平也越强;水合粒径约为1μm的磷酸镧微粒主要通过吞噬作用和巨胞饮以及网格蛋白介导的内吞进入细胞,对其介导的IL-1β分泌贡献较大;但陷窝蛋白介导的内吞途径对具较小水合粒径微粒的细胞摄入以及刺激细胞分泌IL-1β的水平也有较大贡献。研究表明具不同水合粒径大小的稀土微粒可通过不同的跨膜途径进入细胞,从而引起其刺激细胞分泌IL-1β的效应的差异性。这提示微粒的大小以及在体内的入胞方式与稀土微粒引起的炎症反应相关,将为稀土的作用模式以及在胞内分布和转运的方式提供依据,有助于稀土的风险性评估和合理应用。Based on the application status of rare earths, the present study aims to explore the differential effects of lanthanum phosphate particles with various hydrodynamic diameters on IL-1β secretion of macrophages and the relationship with transport processes, using THP-1 macrophages(THP-M) as cellular models. The results demonstrate that the LaCl3 solution can produce LaPO4 particles with different sizes in the cell culture medium containing different concentrations of serums with a wide range of size distribution. The secretion of IL-1βof THP-1 macrophages stimulated by these particles is related to the size of particles. The larger size of the particle exerts the stronger effect. Phagocytosis, macropinocytosis and clathrin-mediated endocytosis play a major role in the secretion of IL-1β stimulated by large particles(~1 μm), while caveolin-mediated endocytosis contributes more to the secretion of IL-1β stimulated by small particles(~500 nm). The present study shows that the lanthanum phosphate particles with various hydrodynamic diameters may enter cells through different transmembrane pathways, resulting in differences in the secretion of IL-1β. The above results indicate that the size of the particles and their transport processes are both related to the inflammatory response. This work will provide the scientific basis for the mode of action, intracellular distribution and transport routes of rare earth elements, and may contribute to their risk evaluation and rational applications.

关 键 词：稀土磷酸盐微粒 巨噬细胞 IL-1Β 内吞 

分 类 号：O614.33[理学—无机化学] Q256[理学—化学]