Wang Ruhung, Lohray Rishabh, Chow Erik, Gangupantula Pratima, Smith Loren, Draper Rockford
Department of Biological Sciences, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, USA.
Department of Chemistry & Biochemistry, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, USA.
Nanomaterials (Basel). 2020 Dec 3;10(12):2417. doi: 10.3390/nano10122417.
The production and applications of multi-walled carbon nanotubes (MWNTs) have increased despite evidence that MWNTs can be toxic. Recently, we reported that the binding of Pluronic F-108 (PF108)-coated carboxylated MWNTs (C-MWNTs) to macrophages is inhibited by class A scavenger receptors (SR-As) antagonists (R. Wang et al., 2018. Nanotoxicology 12:677-690). The current study investigates the uptake of PF108-coated MWNTs by macrophages lacking SR-A1 and by CHO cells that ectopically express SR-A1. Macrophages without SR-A1 failed to take up C-MWNTs and CHO cells that expressed SR-A1 did take up C-MWNTs, but not pristine MWNTs (P-MWNTs) or amino-functionalized MWNTs (N-MWNTs). The dependence of C-MWNT uptake on SR-A1 is strong evidence that SR-A1 is a receptor for C-MWNTs. The consequences of SR-A1-dependent C-MWNT accumulation on cell viability and phagocytic activity in macrophages were also studied. C-MWNTs were more toxic than P-MWNTs and N-MWNTs in cell proliferation and colony formation tests. C-MWNTs reduced surface SR-A1 levels in RAW 264.7 cells and impaired phagocytic uptake of three known SR-A1 ligands, polystyrene beads, heat-killed , and oxLDL. Altogether, results of this study confirmed that SR-A1 receptors are important for the selective uptake of PF108-coated C-MWNTs and that accumulation of the C-MWNTs impairs phagocytic activity and cell viability in macrophages.
尽管有证据表明多壁碳纳米管(MWNTs)可能具有毒性,但其生产和应用仍在增加。最近,我们报道了A类清道夫受体(SR-As)拮抗剂可抑制Pluronic F-108(PF108)包被的羧基化MWNTs(C-MWNTs)与巨噬细胞的结合(R. Wang等人,2018年。《纳米毒理学》12:677-690)。本研究调查了缺乏SR-A1的巨噬细胞和异位表达SR-A1的CHO细胞对PF108包被的MWNTs的摄取情况。缺乏SR-A1的巨噬细胞无法摄取C-MWNTs,而表达SR-A1的CHO细胞能够摄取C-MWNTs,但不能摄取原始MWNTs(P-MWNTs)或氨基功能化MWNTs(N-MWNTs)。C-MWNTs摄取对SR-A1的依赖性有力地证明了SR-A1是C-MWNTs的受体。还研究了SR-A1依赖性C-MWNT积累对巨噬细胞活力和吞噬活性的影响。在细胞增殖和集落形成试验中,C-MWNTs比P-MWNTs和N-MWNTs毒性更大。C-MWNTs降低了RAW 264.7细胞表面SR-A1的水平,并损害了对三种已知SR-A1配体(聚苯乙烯珠、热杀死的[具体物质未明确]和氧化低密度脂蛋白)的吞噬摄取。总之,本研究结果证实SR-A1受体对于PF108包被的C-MWNTs的选择性摄取很重要,并且C-MWNTs的积累会损害巨噬细胞的吞噬活性和细胞活力。