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Am J Physiol Lung Cell Mol Physiol. 2017 Sep 1;313(3):L581-L591. doi: 10.1152/ajplung.00074.2017. Epub 2017 Jun 22.

Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension.

Author information

1
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
2
Marsico Lung Institute, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
3
Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, Maryland; and.
4
Department of Environmental Health and Engineering, School of Public Health, Johns Hopkins University, Baltimore, Maryland.
5
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland; vsidhay1@jhmi.edu.

Abstract

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Cigarette smoke (CS) drives disease development and progression. The epithelial barrier is damaged by CS with increased monolayer permeability. However, the molecular changes that cause this barrier disruption and the interaction between adhesion proteins and the cytoskeleton are not well defined. We hypothesized that CS alters monolayer integrity by increasing cell contractility and decreasing cell adhesion in epithelia. Normal human airway epithelial cells and primary COPD epithelial cells were exposed to air or CS, and changes measured in protein levels. We measured the cortical tension of individual cells and the stiffness of cells in a monolayer. We confirmed that the changes in acute and subacute in vitro smoke exposure reflect protein changes seen in cell monolayers and tissue sections from COPD patients. Epithelial cells exposed to repetitive CS and those derived from COPD patients have increased monolayer permeability. E-cadherin and β-catenin were reduced in smoke exposed cells as well as in lung tissue sections from patients with COPD. Moreover, repetitive CS caused increased tension in individual cells and cells in a monolayer, which corresponded with increased polymerized actin without changes in myosin IIA and IIB total abundance. Repetitive CS exposure impacts the adhesive intercellular junctions and the tension of epithelial cells by increased actin polymer levels, to further destabilize cell adhesion. Similar changes are seen in epithelial cells from COPD patients indicating that these findings likely contribute to COPD pathology.

KEYWORDS:

COPD; E cadherin; cigarette smoke; cortical tension; epithelial barrier

PMID:
28642260
PMCID:
PMC5625260
DOI:
10.1152/ajplung.00074.2017
[Indexed for MEDLINE]
Free PMC Article

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