title: Quantum dots impair macrophagic morphology and the ability of phagocytosis by inhibiting the Rho-associated kinase signaling.
abstract: Quantum dots (QDs) are fluorescent semiconductor nanoparticles that have broad excitation spectra, narrow emission peaks, long fluorescence lifetimes, and the ability to easily conjugate with bio-molecules. Due to these distinct characteristics, QDs represent promising substances in biological imaging and labelling. However, the side and adverse effects of QDs are also widely studied. Herein, we recognize macrophages as the pivotal cells in ingesting QDs, and that the accumulation of QDs inside macrophages leads to significant morphological alterations and a remarkable reduction of their ability to erythrophagocytize in vitro. In a mouse model with chronic exposure to QDs, red blood cell (RBC) retention in spleens and severe splenomegaly were observed, presumably due to attenuated macrophagic erythrophagocytosis in vivo. Importantly, we demonstrated that QDs greatly inhibited the Rho-associated kinase (ROCK) activity, resulting in impaired fidelity of the actin cytoskeleton and actin-rich structure (such as surface protrusions), which was assumed to be the molecular basis underlying the blunted macrophagic morphology and reduced ability to phagocytize. The combined data provide insights into QDs' intracellular trafficking, localization and biological fate in macrophages, and the resultant impairment to cytoskeleton coupled with inhibition on the ROCK signalling would decrease the macrophagic ability to erythrophagocytize with diminished RBC recycling and splenic RBC retention in animals.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Qu
authors.forename: Changwen
authors.initials: C
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.forename: Jiuyang
authors.initials: J
authors.lastname: He
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Sijin
authors.initials: S
authors.lastname: Liu
authors.forename: Guibin
authors.initials: G
authors.lastname: Jiang
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008422:Materials Testing; D051379:Mice; D008954:Models, Biological; D010587:Phagocytosis / Q000187:drug effects*; D045663:Quantum Dots; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D054460:rho-Associated Kinases