Document Detail


Differential expression of syndecan-1 mediates cationic nanoparticle toxicity in undifferentiated versus differentiated normal human bronchial epithelial cells.
MedLine Citation:
PMID:  21366263     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 ENMs. 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 (NHBE) cells to cationic mesoporous silica nanoparticles (MSNPs) 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, using a multiparametric assay that screens for an integrated set of sublethal and lethal response outcomes. MSNPs 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. Pretreatment 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.
Authors:
Haiyuan Zhang; Tian Xia; Huan Meng; Min Xue; Saji George; Zhaoxia Ji; Xiang Wang; Rong Liu; Meiying Wang; Bryan France; Robert Rallo; Robert Damoiseaux; Yoram Cohen; Kenneth A Bradley; Jeffrey I Zink; Andre E Nel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-03-02
Journal Detail:
Title:  ACS nano     Volume:  5     ISSN:  1936-086X     ISO Abbreviation:  ACS Nano     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-26     Completed Date:  2011-07-28     Revised Date:  2014-02-03    
Medline Journal Info:
Nlm Unique ID:  101313589     Medline TA:  ACS Nano     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2756-69     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Bronchi / cytology,  drug effects*,  metabolism
Cations*
Cell Differentiation*
Cells, Cultured
Epithelial Cells / drug effects,  metabolism
Erythrocytes / drug effects
Hemolysis / drug effects
Humans
Microscopy, Confocal
Microscopy, Electron, Transmission
Nanoparticles*
Syndecan-1 / metabolism*
Grant Support
ID/Acronym/Agency:
R01 CA133697/CA/NCI NIH HHS; R01 ES016746/ES/NIEHS NIH HHS; R01 ES016746/ES/NIEHS NIH HHS; RC2 ES018766/ES/NIEHS NIH HHS; RC2 ES018766/ES/NIEHS NIH HHS; U19 ES019528/ES/NIEHS NIH HHS; U19 ES019528/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Cations; 0/Syndecan-1
Comments/Corrections

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