Document Detail

Side-specific effects by cadmium exposure: apical and basolateral treatment in a coculture model of the blood-air barrier.
MedLine Citation:
PMID:  20399800     Owner:  NLM     Status:  MEDLINE    
Cadmium (Cd(2+)) is a widespread environmental pollutant, which is associated with a wide variety of cytotoxic and metabolic effects. Recent studies showed that intoxication with the heavy metal most importantly targets the integrity of the epithelial barrier. In our study, the lung epithelial cell line, NCI H441, was cultured with the endothelial cell line, ISO-HAS-1, as a bilayer on a 24-well HTS-Transwell filter plate. This coculture model was exposed to various concentrations of CdCl(2). The transepithelial electrical resistance decreased on the apical side only after treatment with high Cd(2+) concentrations after 48 h. By contrast, a breakdown of TER to less than 5% of baseline could be observed much earlier (after 24 h) when Cd(2+) was administered from the basal side. Observations of cell layer fragmentation and widening of intercellular spaces confirmed the barrier breakdown only for the basolaterally treated samples. Furthermore, the cytotoxicity and release of proinflammatory markers was enhanced if samples were exposed to Cd(2+) from the basal side compared to treatment from the apical side. Moreover, we could demonstrate that a high concentration of Ca(2+) could prevent the barrier-disrupting effect of Cd(2+). In conclusion, the exposure of Cd(2+) to cocultures of lung cells caused a decrease in TER, major morphological changes, a reduction of cell viability and an increase of cytokine release, but the effects markedly differed between the two modes of exposure. Therefore, our results suggest that intact epithelial TJs may play a major role in protecting the air-blood barrier from inhaled Cd(2+).
Mirko Papritz; Christine Pohl; Christoph W?bbeke; Michaela Moisch; Helene Hofmann; Maria Iris Hermanns; Horst Thiermann; Charles James Kirkpatrick; Kai Kehe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-23
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  245     ISSN:  1096-0333     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-21     Completed Date:  2010-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  361-9     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Bundeswehr Institute of Pharmacology and Toxicology Munich, Germany.
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MeSH Terms
Adherens Junctions / drug effects,  pathology
Blood-Air Barrier / drug effects*,  immunology,  pathology
Cadmium Chloride / toxicity*
Calcium / metabolism
Cell Line, Tumor
Cell Polarity*
Cell Shape / drug effects
Cell Survival / drug effects
Coculture Techniques
Cytokines / metabolism
Dose-Response Relationship, Drug
Electric Impedance
Endothelial Cells / drug effects*,  immunology,  pathology
Epithelial Cells / drug effects*,  immunology,  pathology
Inflammation Mediators / metabolism
Tight Junctions / drug effects,  pathology
Time Factors
Reg. No./Substance:
0/Cytokines; 0/Inflammation Mediators; 10108-64-2/Cadmium Chloride; 7440-70-2/Calcium

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

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