Document Detail


Interaction and localization of synthetic nanoparticles in healthy and cystic fibrosis airway epithelial cells: effect of ozone exposure.
MedLine Citation:
PMID:  22007674     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Nanoparticles (NPs) produced by nanotechnology processes have taken the field of medicine by storm. Concerns about safety of these NPs in humans, however, have recently been raised. Although studies of NP toxicity have focused on lung disease the mechanistic link between NP exposure and lung injury remained unclear. This is primarily due to a lack of availability of appropriate airway disease models and sophisticated microscopic techniques to study nano-sized particulate delivery and resulting responses.
METHODS: Air-liquid interface (ALI) cultures of non-cystic fibrosis (CF) and CF airway epithelial cells were exposed to the FITC-labeled NPs using a PennCentury microsprayer™. Uptake of NPs was assessed by FACS. Laser scanning microscopy (LSM) was performed and the images were analyzed by an advanced imaging software to study particle deposition and uptake.
RESULTS: Flow cytometry data revealed that CF cells accumulated increased amounts of NPs. The increased NP uptake could be attributed to the reduced CF transmembrane conductance regulator (CFTR) function as a similar increased retention/uptake was observed in cells whose CFTR expression was downregulated by antisense oligonucleotide. NPs alone did not induce pro-inflammatory cytokine release or cell death. The cell culture system was sensitive to ozone but exposure to the uncoated synthetic NPs used in this study, did not cause any synergistic or suppressive effects. LSM imaging and subsequent image restoration further indicated particle uptake and intracellular localization. Exposure to ozone increased nuclear uptake in both non-CF and CF cells.
CONCLUSION: Our findings demonstrate the uptake of NPs using ALI cultures of non-CF and CF airway epithelial cells. The NPs used here were useful in demonstrating uptake by airway epithelial cells without causing adverse effects in presence or absence of ozone. However, to totally exclude toxic effects, chronic studies under in vivo conditions using coated particulates are required.
Authors:
Shama Ahmad; David O Raemy; Joan E Loader; Jenai M Kailey; Keith B Neeves; Carl W White; Aftab Ahmad; Peter Gehr; Barbara M Rothen-Rutishauser
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-18
Journal Detail:
Title:  Journal of aerosol medicine and pulmonary drug delivery     Volume:  25     ISSN:  1941-2703     ISO Abbreviation:  J Aerosol Med Pulm Drug Deliv     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-07     Completed Date:  2012-06-11     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101475057     Medline TA:  J Aerosol Med Pulm Drug Deliv     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7-15     Citation Subset:  T    
Affiliation:
Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. ahmads@njhealth.org
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MeSH Terms
Descriptor/Qualifier:
Bronchi / drug effects*,  metabolism
Cells, Cultured
Cystic Fibrosis / metabolism*
Cystic Fibrosis Transmembrane Conductance Regulator / physiology
Cytokines / biosynthesis
Electric Impedance
Epithelial Cells / drug effects,  metabolism
Humans
Microscopy, Electron, Scanning
Nanoparticles* / toxicity
Ozone / toxicity*
Grant Support
ID/Acronym/Agency:
K12 KL2RR025779/RR/NCRR NIH HHS; R01-ES014448/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/CFTR protein, human; 0/Cytokines; 10028-15-6/Ozone; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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