title: Amphiphilic polymer-coated CdSe/ZnS quantum dots induce pro-inflammatory cytokine expression in mouse lung epithelial cells and macrophages.
abstract: Quantum dots (Qdots) are semiconductor nanoparticles with size-tunable fluorescence capabilities with diverse applications. Qdots typically contain cadmium or other heavy metals, hence raising concerns of their potential toxicity, especially in occupational settings where inhalation of nanomaterials may increase the risk of lung disease. Accordingly, we assessed the effects of tri-n-octylphosphine oxide, poly(maleic anhydride-alt-1-tetradecene) (TOPO-PMAT) coated CdSe/ZnS Qdots on mouse lung epithelial cells and macrophages. Mouse tracheal epithelial cells (MTEC), grown as organotypic cultures, bone marrow-derived macrophages (BMDM), and primary alveolar macrophages (AM) were derived from C57BL/6J or A/J mice and treated with TOPO-PMAT CdSe/ZnS Qdots (10-160 nM) for up to 24 h. Cadmium analysis showed that Qdots remained in the apical compartment of MTEC cultures, whereas they were avidly internalized by AM and BMDM, which did not differ between strains. In MTEC, Qdots selectively induced expression (mRNA and protein) of neutrophil chemokines CXCL1 and CXCL2 but only low to no detectable levels of other factors assessed. In contrast, 4 h exposure to Qdots markedly increased expression of CXCL1, IL6, IL12, and other pro-inflammatory factors in BMDM. Higher inflammatory response was seen in C57BL/6J than in A/J BMDM. Similar expression responses were observed in AM, although overall levels were less robust than in BMDM. MTEC from A/J mice were more sensitive to Qdot pro-inflammatory effects while macrophages from C57BL/6J mice were more sensitive. These findings suggest that patterns of Qdot-induced pulmonary inflammation are likely to be cell-type specific and genetic background dependent.
authors.affiliation: Center for Lung Biology, University of Washington , Seattle, WA , United States .
authors.forename: Vivian
authors.initials: V
authors.lastname: Lee
authors.forename: Ryan S
authors.initials: RS
authors.lastname: McMahan
authors.forename: Xiaoge
authors.initials: X
authors.lastname: Hu
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Gao
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Faustman
authors.forename: William C
authors.initials: WC
authors.lastname: Griffith
authors.forename: Terrance J
authors.initials: TJ
authors.lastname: Kavanagh
authors.forename: David L
authors.initials: DL
authors.lastname: Eaton
authors.forename: John K
authors.initials: JK
authors.lastname: McGuire
authors.forename: William C
authors.initials: WC
authors.lastname: Parks
mesh_terms: D000818:Animals; D019187:Cadmium Compounds / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D045663:Quantum Dots; D018036:Selenium Compounds / Q000633:toxicity*; D013440:Sulfides / Q000633:toxicity*; D017967:Zinc Compounds / Q000633:toxicity*
chemical_list: D019187:Cadmium Compounds; D016207:Cytokines; D018836:Inflammation Mediators; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; C058667:cadmium selenide; C031238:zinc sulfide
keywords: Engineered nanomaterial; in vitro toxicity; pulmonary inflammation