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

TitleCigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension.
Publication TypePublication
Year2017
AuthorsNishida K, Brune KA, Putcha N, Mandke P, O'Neal WK, Shade D, Srivastava V, Wang M, Lam H, An SS, M Drummond B, Hansel NN, Robinson DN, Sidhaye VK
JournalAm J Physiol Lung Cell Mol Physiol
Volume313
Issue3
PaginationL581-L591
Date Published2017 Sep 01
ISSN1522-1504
KeywordsAdherens Junctions, Aged, Biomechanical Phenomena, Cadherins, Cell Adhesion, Cell Death, Cell Membrane Permeability, Cytoskeleton, Epithelial Cells, Female, Humans, Male, Middle Aged, Myosin Type II, Pulmonary Disease, Chronic Obstructive, smoking
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.

DOI10.1152/ajplung.00074.2017
Alternate JournalAm. J. Physiol. Lung Cell Mol. Physiol.
PubMed ID28642260
PubMed Central IDPMC5625260
Grant ListHHSN268200900019C / HL / NHLBI NIH HHS / United States
R01 GM066817 / GM / NIGMS NIH HHS / United States
R01 HL125000 / HL / NHLBI NIH HHS / United States
R01 HL124099 / HL / NHLBI NIH HHS / United States
R01 HL107361 / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
MS#: 
MS045
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Baltimore (Johns Hopkins University)
ECI: 
Manuscript Status: 
Published