Side-specific effects by cadmium exposure: Apical and basolateral treatment in a coculture model of the blood-air barrier

Papritz, Mirko; Pohl, Christine; Wuebbeke, Christoph; Moisch, Michaela; Hofmann, Helene; Hermanns, Maria Iris; Thiermann, Horst; Kirkpatrick, Charles James; Kehe, Kai

doi:10.1016/j.taap.2010.04.002

Title: Side-specific effects by cadmium exposure: Apical and basolateral treatment in a coculture model of the blood-air barrier

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Abstract

Cadmium (Cd{sup 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 (registered) filter plate. This coculture model was exposed to various concentrations of CdCl{sub 2}. The transepithelial electrical resistance decreased on the apical side only after treatment with high Cd{sup 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{sup 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{sup 2+} from the basal side compared to treatment from the apical side. Moreover, we could demonstrate that a high concentration of Ca{sup 2+} could prevent the barrier-disrupting effect of Cd{sup 2+}. In conclusion, the exposure of Cd{sup 2+}more »« less

Authors:

Papritz, Mirko ^[1]; Pohl, Christine ^[2]; Wuebbeke, Christoph ^[1]; Moisch, Michaela; Hofmann, Helene; Hermanns, Maria Iris ^[2]; Thiermann, Horst ^[1]; Kirkpatrick, Charles James ^[2]; Kehe, Kai ^[1]

Bundeswehr Institute of Pharmacology and Toxicology Munich (Germany)
Institute of Pathology, Johannes Gutenberg University Mainz (Germany)

Publication Date:: Tue Jun 15 00:00:00 EDT 2010

OSTI Identifier:: 21460181

Resource Type:: Journal Article

Journal Name:: Toxicology and Applied Pharmacology

Additional Journal Information:: Journal Volume: 245; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2010.04.002; PII: S0041-008X(10)00129-8; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0041-008X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; AIR; BLOOD; CADMIUM; CADMIUM IONS; ELECTRIC CONDUCTIVITY; FRAGMENTATION; LUNGS; MORPHOLOGICAL CHANGES; RESPIRATORY TRACT CELLS; TOXICITY; ANIMAL CELLS; BIOLOGICAL MATERIALS; BODY; BODY FLUIDS; CHARGED PARTICLES; ELECTRICAL PROPERTIES; ELEMENTS; FLUIDS; GASES; IONS; MATERIALS; METALS; ORGANS; PHYSICAL PROPERTIES; RESPIRATORY SYSTEM; SOMATIC CELLS

Citation Formats


                    Papritz, Mirko, Institute of Pathology, Johannes Gutenberg University Mainz, Pohl, Christine, Wuebbeke, Christoph, Moisch, Michaela, Hofmann, Helene, Hermanns, Maria Iris, Thiermann, Horst, Kirkpatrick, Charles James, and Kehe, Kai. Side-specific effects by cadmium exposure: Apical and basolateral treatment in a coculture model of the blood-air barrier.  United States: N. p., 2010. 
        Web.  doi:10.1016/j.taap.2010.04.002.

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                    Papritz, Mirko, Institute of Pathology, Johannes Gutenberg University Mainz, Pohl, Christine, Wuebbeke, Christoph, Moisch, Michaela, Hofmann, Helene, Hermanns, Maria Iris, Thiermann, Horst, Kirkpatrick, Charles James, & Kehe, Kai. Side-specific effects by cadmium exposure: Apical and basolateral treatment in a coculture model of the blood-air barrier.  United States.  https://doi.org/10.1016/j.taap.2010.04.002

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                    Papritz, Mirko, Institute of Pathology, Johannes Gutenberg University Mainz, Pohl, Christine, Wuebbeke, Christoph, Moisch, Michaela, Hofmann, Helene, Hermanns, Maria Iris, Thiermann, Horst, Kirkpatrick, Charles James, and Kehe, Kai. 2010.  
        "Side-specific effects by cadmium exposure: Apical and basolateral treatment in a coculture model of the blood-air barrier".  United States.  https://doi.org/10.1016/j.taap.2010.04.002.

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@article{osti_21460181,

  title        = {Side-specific effects by cadmium exposure: Apical and basolateral treatment in a coculture model of the blood-air barrier},

  author       = {Papritz, Mirko and Institute of Pathology, Johannes Gutenberg University Mainz and Pohl, Christine and Wuebbeke, Christoph and Moisch, Michaela and Hofmann, Helene and Hermanns, Maria Iris and Thiermann, Horst and Kirkpatrick, Charles James and Kehe, Kai},

  abstractNote = {Cadmium (Cd{sup 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 (registered) filter plate. This coculture model was exposed to various concentrations of CdCl{sub 2}. The transepithelial electrical resistance decreased on the apical side only after treatment with high Cd{sup 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{sup 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{sup 2+} from the basal side compared to treatment from the apical side. Moreover, we could demonstrate that a high concentration of Ca{sup 2+} could prevent the barrier-disrupting effect of Cd{sup 2+}. In conclusion, the exposure of Cd{sup 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{sup 2+}.},

  doi          = {10.1016/j.taap.2010.04.002},

  url          = {https://www.osti.gov/biblio/21460181},
  journal      = {Toxicology and Applied Pharmacology},

  issn         = {0041-008X},

  number       = 3,

  volume       = 245,

  place        = {United States},

  year         = {Tue Jun 15 00:00:00 EDT 2010},

  month        = {Tue Jun 15 00:00:00 EDT 2010}

}

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