High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion

Leena P. Desai, Scott Sinclair, Kenneth E. Chapman, Aviv Hassid, Christopher Waters

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Patients with acute respiratory distress syndrome undergoing mechanical ventilation may be exposed to both high levels of stretch and high levels of oxygen. We hypothesized that the combination of high stretch and hyperoxia promotes loss of epithelial adhesion and impairs epithelial repair mechanisms necessary for restoration of barrier function. We utilized a model of high tidal volume mechanical ventilation (25 ml/kg) with hyperoxia (50% O2) in rats to investigate alveolar type II (AT2) cell adhesion and focal adhesion signaling. AT2 cells isolated from rats exposed to hyperoxia and high tidal volume mechanical ventilation (MVHO) exhibited significantly decreased cell adhesion and reduction in phosphotyrosyl levels of focal adhesion kinase (FAK) and paxillin compared with control rats, rats exposed to hyperoxia without ventilation (HO), or rats ventilated with normoxia (MV). MV alone increased phosphorylation of p130Cas. RhoA activation was increased by MV, HO, and the combination of MV and HO. Treatment of MVHO cells with keratinocyte growth factor (KGF) for 1 h upon isolation reduced RhoA activity and restored attachment to control levels. Attachment and migration of control AT2 cells was significantly decreased by constitutively active RhoA or a kinase inactive form of FAK (FRNK), whereas expression of dominant negative RhoA in cells from MVHO-treated rats restored cell adhesion. Mechanical ventilation with hyperoxia promotes changes in focal adhesion proteins and RhoA in AT2 cells that may be deleterious for cell adhesion and migration.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume293
Issue number3
DOIs
StatePublished - Sep 1 2007

Fingerprint

Alveolar Epithelial Cells
Hyperoxia
Tidal Volume
Artificial Respiration
Cell Adhesion
Focal Adhesion Protein-Tyrosine Kinases
Focal Adhesions
rhoA GTP-Binding Protein
Fibroblast Growth Factor 7
Paxillin
Adult Respiratory Distress Syndrome
Cell Movement
Ventilation
Phosphotransferases
Phosphorylation
Oxygen

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion. / Desai, Leena P.; Sinclair, Scott; Chapman, Kenneth E.; Hassid, Aviv; Waters, Christopher.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 293, No. 3, 01.09.2007.

Research output: Contribution to journalArticle

@article{62b4f0b5f1a749abab5f2448c841d922,
title = "High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion",
abstract = "Patients with acute respiratory distress syndrome undergoing mechanical ventilation may be exposed to both high levels of stretch and high levels of oxygen. We hypothesized that the combination of high stretch and hyperoxia promotes loss of epithelial adhesion and impairs epithelial repair mechanisms necessary for restoration of barrier function. We utilized a model of high tidal volume mechanical ventilation (25 ml/kg) with hyperoxia (50{\%} O2) in rats to investigate alveolar type II (AT2) cell adhesion and focal adhesion signaling. AT2 cells isolated from rats exposed to hyperoxia and high tidal volume mechanical ventilation (MVHO) exhibited significantly decreased cell adhesion and reduction in phosphotyrosyl levels of focal adhesion kinase (FAK) and paxillin compared with control rats, rats exposed to hyperoxia without ventilation (HO), or rats ventilated with normoxia (MV). MV alone increased phosphorylation of p130Cas. RhoA activation was increased by MV, HO, and the combination of MV and HO. Treatment of MVHO cells with keratinocyte growth factor (KGF) for 1 h upon isolation reduced RhoA activity and restored attachment to control levels. Attachment and migration of control AT2 cells was significantly decreased by constitutively active RhoA or a kinase inactive form of FAK (FRNK), whereas expression of dominant negative RhoA in cells from MVHO-treated rats restored cell adhesion. Mechanical ventilation with hyperoxia promotes changes in focal adhesion proteins and RhoA in AT2 cells that may be deleterious for cell adhesion and migration.",
author = "Desai, {Leena P.} and Scott Sinclair and Chapman, {Kenneth E.} and Aviv Hassid and Christopher Waters",
year = "2007",
month = "9",
day = "1",
doi = "10.1152/ajplung.00127.2007",
language = "English (US)",
volume = "293",
journal = "American Journal of Physiology - Lung Cellular and Molecular Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion

AU - Desai, Leena P.

AU - Sinclair, Scott

AU - Chapman, Kenneth E.

AU - Hassid, Aviv

AU - Waters, Christopher

PY - 2007/9/1

Y1 - 2007/9/1

N2 - Patients with acute respiratory distress syndrome undergoing mechanical ventilation may be exposed to both high levels of stretch and high levels of oxygen. We hypothesized that the combination of high stretch and hyperoxia promotes loss of epithelial adhesion and impairs epithelial repair mechanisms necessary for restoration of barrier function. We utilized a model of high tidal volume mechanical ventilation (25 ml/kg) with hyperoxia (50% O2) in rats to investigate alveolar type II (AT2) cell adhesion and focal adhesion signaling. AT2 cells isolated from rats exposed to hyperoxia and high tidal volume mechanical ventilation (MVHO) exhibited significantly decreased cell adhesion and reduction in phosphotyrosyl levels of focal adhesion kinase (FAK) and paxillin compared with control rats, rats exposed to hyperoxia without ventilation (HO), or rats ventilated with normoxia (MV). MV alone increased phosphorylation of p130Cas. RhoA activation was increased by MV, HO, and the combination of MV and HO. Treatment of MVHO cells with keratinocyte growth factor (KGF) for 1 h upon isolation reduced RhoA activity and restored attachment to control levels. Attachment and migration of control AT2 cells was significantly decreased by constitutively active RhoA or a kinase inactive form of FAK (FRNK), whereas expression of dominant negative RhoA in cells from MVHO-treated rats restored cell adhesion. Mechanical ventilation with hyperoxia promotes changes in focal adhesion proteins and RhoA in AT2 cells that may be deleterious for cell adhesion and migration.

AB - Patients with acute respiratory distress syndrome undergoing mechanical ventilation may be exposed to both high levels of stretch and high levels of oxygen. We hypothesized that the combination of high stretch and hyperoxia promotes loss of epithelial adhesion and impairs epithelial repair mechanisms necessary for restoration of barrier function. We utilized a model of high tidal volume mechanical ventilation (25 ml/kg) with hyperoxia (50% O2) in rats to investigate alveolar type II (AT2) cell adhesion and focal adhesion signaling. AT2 cells isolated from rats exposed to hyperoxia and high tidal volume mechanical ventilation (MVHO) exhibited significantly decreased cell adhesion and reduction in phosphotyrosyl levels of focal adhesion kinase (FAK) and paxillin compared with control rats, rats exposed to hyperoxia without ventilation (HO), or rats ventilated with normoxia (MV). MV alone increased phosphorylation of p130Cas. RhoA activation was increased by MV, HO, and the combination of MV and HO. Treatment of MVHO cells with keratinocyte growth factor (KGF) for 1 h upon isolation reduced RhoA activity and restored attachment to control levels. Attachment and migration of control AT2 cells was significantly decreased by constitutively active RhoA or a kinase inactive form of FAK (FRNK), whereas expression of dominant negative RhoA in cells from MVHO-treated rats restored cell adhesion. Mechanical ventilation with hyperoxia promotes changes in focal adhesion proteins and RhoA in AT2 cells that may be deleterious for cell adhesion and migration.

UR - http://www.scopus.com/inward/record.url?scp=34548405551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548405551&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00127.2007

DO - 10.1152/ajplung.00127.2007

M3 - Article

VL - 293

JO - American Journal of Physiology - Lung Cellular and Molecular Physiology

JF - American Journal of Physiology - Lung Cellular and Molecular Physiology

SN - 1040-0605

IS - 3

ER -