Journal article
Ambient particulate matter affects occludin distribution and increases alveolar transepithelial electrical conductance
Respirology (Carlton, Vic.), Vol.16(2), pp.340-349
02/01/2011
DOI: 10.1111/j.1440-1843.2010.01910.x
PMCID: PMC3625061
PMID: 21122029
Abstract
Background and objective: Inhaled particulate matter (PM) causes lung inflammation and epithelial dysfunction. However, the direct effect of PM on alveolar epithelial barrier integrity is not well understood. Our aim is to determine whether PM exposure affects the alveolar epithelial cells (AEC) transepithelial electrical conductance (Gt) and tight junction (TJ) proteins.
Methods: Human AEC (A549) and primary rat AEC were exposed to PM of <10 mu m size (PM10) and diesel exhaust particles (DEP), using titanium dioxide (TiO2) as a control for particle size effects. Gt and permeability to fluorescein isothiocyanate-dextran (FITC-Dextran) were measured to assess barrier integrity. TJ integrity was evaluated by analysing penetration of Lanthanum nitrate (La3+) under transmission electron microscopy. Surface proteins were labelled with biotin and analysed by western blot. Immunofluorescence was performed to assess colocalization of TJ proteins including occludin and zonula occludens-1 (ZO-1). PM induced dissociation of occludin-ZO-1 was evaluated by co-immunoprecipitation.
Results: PM10 and DEP increased Gt and disrupted TJ after 3 h of treatment. PM10 and DEP induced occludin internalization from the plasma membrane into endosomal compartments and dissociation of occludin from ZO-1. Overexpression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and catalase, prevented PM-induced Gt increase, occludin reduction from the plasmamembrane and its dissociation from ZO-1.
Conclusions: PM induces alveolar epithelial dysfunction in part via occludin reduction at the plasmamembrane and ZO-1 dissociation in AEC. Furthermore, these effects are prevented by overexpression of two different antioxidant enzymes.
Details
- Title: Subtitle
- Ambient particulate matter affects occludin distribution and increases alveolar transepithelial electrical conductance
- Creators
- Juan C. Caraballo - University of IowaCecilia Yshii - University of IowaWhitney Westphal - University of IowaThomas Moninger - University of IowaAlejandro P. Comellas - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Respirology (Carlton, Vic.), Vol.16(2), pp.340-349
- DOI
- 10.1111/j.1440-1843.2010.01910.x
- PMID
- 21122029
- PMCID
- PMC3625061
- NLM abbreviation
- Respirology
- ISSN
- 1323-7799
- eISSN
- 1440-1843
- Publisher
- Wiley
- Number of pages
- 10
- Grant note
- P30 ES05605 / NIEHS/NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) K01HL080966 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P30ES005605 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) K01HL080966 / NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 02/01/2011
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
- Record Identifier
- 9984359881202771
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