中国动脉硬化杂志2026，Vol.34Issue(7)：621-632,12.DOI:10.20039/j.cnki.1007-3949.2026.07.004
S1P/S1PR1通过上调TAM受体和吞噬相关蛋白表达增强巨噬细胞胞葬作用
S1P/S1PR1 enhances macrophage efferocytosis by upregulating the expression of TAM receptors and phagocytosis-related proteins
摘要
Abstract
Aim To investigate whether sphingosine-1-phosphate(S1P)promotes LC3-associated phagocytosis via its receptor S1PR1,thereby enhancing the efferocytosis of THP-1-derived macrophages.Methods THP-1 mono-cytes were induced to differentiate into macrophages using 80 μg/L phorbol ester;254 nm ultraviolet radiation was used to induce early apoptosis in Jurkat cells for cell phagocytosis experiments.Macrophages were treated with 0,0.5,1.0 and 1.5 μmol/L S1P for 12 h,or treated with 1.5 μmol/L S1P alone or in combination with S1PR1 antagonist W146,S1PR2 antagonist JTE-013,S1PR3 antagonist CAY10444 and ATG4B inhibitor NSC185058.Western blot was used to detect the expression levels of MerTK,Axl,Tyro3,LC3B and LAMP1,fluorescence-labeled apoptotic cells were applied in phagocy-tosis assays to evaluate phagocytic efficiency,ELISA was employed to measure the levels of pro-inflammatory factors(TNF-α,IL-6 and IL-1β)and anti-inflammatory factors(TGF-β,IL-4 and IL-10)in the supernatant.Results S1P could significantly enhance the phagocytic capacity of macrophages for apoptotic cells,and this effect was concentration-de-pendent.Specifically,the phagocytic efficiency of macrophages for apoptotic cells was significantly improved(P<0.01);the expression of cell burial receptors MerTK,Axl and Tyro3 was markedly upregulated(P<0.01);at the same time,levels of anti-inflammatory factors(TGF-β,IL-4 and IL-10)increased(P<0.01),while pro-inflammatory factors(TNF-α,IL-6 and IL-1β)decreased(P<0.01).The results of the S1P blockade experiment showed that blocking S1PR1 with W146 could reverse the efferocytosis of S1P(P<0.05),while blocking S1PR2 or S1PR3 had no significant effect.S1P treatment significantly increased the gene and protein expression levels of LC3B and LAMP1 in macrophages(P<0.01)and promoted lysosome maturation.After NSC185058 treatment,the phagocytic efficiency and anti-inflammatory factor secretion of macrophages decreased(P<0.05).In addition,the inhibitory effect of blocking S1PR1 and LC3-related phagocytosis on efferocytosis was more significant(P<0.01).Conclusion S1P significantly enhances the phagocytic clearance ability of THP-1-derived macrophages towards apoptotic cells through S1PR1-mediated LC3-related phagocytosis,and promotes the transformation of macrophages into anti-inflammatory phenotypes.关键词
1-磷酸鞘氨醇/1-磷酸鞘氨醇受体1/TAM 受体/胞葬作用/巨噬细胞/吞噬相关蛋白Key words
sphingosine-1-phosphate/sphingosine-1-phosphate receptor 1/TAM receptor/efferocytosis/macrophage/phagocytosis-related protein分类
医药卫生引用本文复制引用
杨皓天,李朝荃,李婧,付傲妮,刘婉婷,雷偲,谢玉鑫,易光辉..S1P/S1PR1通过上调TAM受体和吞噬相关蛋白表达增强巨噬细胞胞葬作用[J].中国动脉硬化杂志,2026,34(7):621-632,12.基金项目
国家自然科学基金项目(81770490) （81770490）
湖南省科技计划项目(2020JJ4535) （2020JJ4535）
