Abstract |
Ten to 25% of adult asthma is occupational induced, a subtype caused by exposure to workplace chemicals. A recent genomewide association study identified single-nucleotide polymorphisms in the cardiac protein αT- catenin (αT-cat) that correlated with the incidence and severity of toluene diisocyanate (TDI) occupational asthma. αT-cat is a critical mediator of cell-cell adhesion and is predominantly expressed in cardiomyocytes, but its connection to asthma remains unknown. Therefore, we sought to determine the primary αT-cat-expressing cell type in the lung and its contribution to lung physiology in a murine model of TDI asthma. We show that αT-cat is expressed in lung within the cardiac sheath of pulmonary veins. Mechanically ventilated αT-cat knockout (KO) mice exhibit a significantly increased pressure-volume curve area compared with wild-type (WT) mice, suggesting that αT-cat loss affects lung hysteresis. Using a murine model of TDI asthma, we find that αT-cat KO mice show increased airway hyperresponsiveness to methacholine compared with WT mice. Bronchoalveolar lavage reveals only a mild macrophage-dominant inflammation that is not significantly different between WT and KO mice. These data suggest that αT-cat may contribute to asthma through a mechanism independent of inflammation and related to heart and pulmonary vein dysfunction.
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Authors | Stephen Sai Folmsbee, Luisa Morales-Nebreda, Jolanda Van Hengel, Koen Tyberghein, Frans Van Roy, G R Scott Budinger, Paul J Bryce, Cara J Gottardi |
Journal | American journal of physiology. Lung cellular and molecular physiology
(Am J Physiol Lung Cell Mol Physiol)
Vol. 308
Issue 3
Pg. L253-8
(Feb 01 2015)
ISSN: 1522-1504 [Electronic] United States |
PMID | 25480337
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 the American Physiological Society. |
Chemical References |
- Air Pollutants
- CTNNA3 protein, mouse
- alpha Catenin
- Toluene 2,4-Diisocyanate
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Topics |
- Air Pollutants
(toxicity)
- Animals
- Asthma, Occupational
(chemically induced, metabolism)
- Cells, Cultured
- Female
- Humans
- Intercellular Junctions
(metabolism)
- Lung
(blood supply, metabolism, pathology)
- Mice, Inbred C57BL
- Mice, Knockout
- Myocytes, Cardiac
(metabolism)
- Pulmonary Veins
(metabolism, pathology)
- Toluene 2,4-Diisocyanate
(toxicity)
- alpha Catenin
(metabolism)
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