Differential expression of syndecan-1 mediates cationic nanoparticle toxicity in undifferentiated versus differentiated normal human bronchial epithelial cells.
Differential expression of syndecan-1 mediates cationic nanoparticle toxicity in undifferentiated versus differentiated normal human bronchial epithelial cells.
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DOI：
10.1021/nn200328m
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发表时间：
2011-04-26
期刊：
影响因子：
17.1
通讯作者：
Nel AE
中科院分区：
文献类型：
--
作者：
Zhang H;Xia T;Meng H;Xue M;George S;Ji Z;Wang X;Liu R;Wang M;France B;Rallo R;Damoiseaux R;Cohen Y;Bradley KA;Zink JI;Nel AE
Most in vitro toxicity studies on engineered nanomaterials (ENMs) use transformed rather than primary cells for logistical reasons. However, primary cells may provide a more appropriate connection to in vivo toxicity because these cells maintain their phenotypic fidelity and are also capable of differentiating into lineages that may be differently affected by potentially hazardous ENM. Few studies to date have focused on the role of cellular differentiation in determining ENM toxicity. We compared the response of undifferentiated and differentiated primary human bronchial epithelial cells (NHBE) to cationic mesoporous silica nanoparticles (MSNP) that are coated with polyethyleneimine (PEI) since this polymer is known to exert differential cytotoxicity depending on its molecular weight and cationic density. The attachment of cationic PEI polymers to the MSNP surface was used to assess these materials' toxicological potential in undifferentiated and differentiated human bronchial epithelial cells (NHBE), using of a multi-parametric assay that screens for an integrated set of sub-lethal and lethal response outcomes. MSNP coated with high molecular weight (10 and 25 kD) polymers were more toxic in differentiated cells than particles coated with shorter length polymers. The increased susceptibility of the differentiated cells is in agreement with more abundant expression of a proteoglycan, syndecan-1, which contains copious heparin sulfate side chains. Pre-treatment with heparinase to remove the negatively charged sulfates decreased MSNP-PEI binding to the cell surface and lowered the cytotoxic potential of the cationic particles. These data demonstrate the importance of studying cellular differentiation as an important variable in the response of primary cells to toxic ENM properties.
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