Epidermal Growth Factor receptor (EGFR) regulates mechanical ventilation-induced lung injury in mice

Alexis Bierman, Adi Yerrapureddy, Narsa M. Reddy, Paul M Hassoun, Sekhar P. Reddy

Research output: Contribution to journalArticle

Abstract

Mechanical ventilation (MV) is used as therapy to support critically ill patients; however, the mechanisms by which MV induces lung injury and inflammation remain unclear. Epidermal growth factor receptor (EGFR)-mediated signaling plays a key role in various physiologic and pathologic processes, which include those modulated by mechanical and shear forces, in various cell types. We hypothesized that EGFR-activated signaling plays a key role in ventilator-induced lung injury and inflammation (VILI). To test this hypothesis, we assessed lung vascular and alveolar permeability as well as inflammation, which are cardinal features of VILI, in mice treated with the EGFR inhibitor AG1478. Inhibition of EGFR activity greatly diminished MV-induced lung alveolar permeability and neutrophil accumulation in the bronchoalveolar lavage (BAL) fluid, as compared with vehicle-treated controls. Similarly, AG1478 inhibition diminished lung vascular leak (as assessed by Evans blue extravasation), but it did not affect interstitial neutrophil accumulation. Inhibition of the EGFR pathway also blocked expression of genes induced by MV. However, intratracheal instillation of EGF alone failed to induce lung injury. Collectively, our findings suggest that EGFR-activated signaling is necessary but not sufficient to produce acute lung injury in mice.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalTranslational Research
Volume152
Issue number6
DOIs
StatePublished - Dec 2008

Fingerprint

Lung Injury
Artificial Respiration
Epidermal Growth Factor Receptor
Ventilator-Induced Lung Injury
Pneumonia
Lung
Neutrophils
Evans Blue
Acute Lung Injury
Bronchoalveolar Lavage Fluid
Capillary Permeability
Pathologic Processes
Epidermal Growth Factor
Critical Illness
Blood Vessels
Permeability
Genes
Inflammation
Gene Expression
Fluids

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, medical
  • Public Health, Environmental and Occupational Health

Cite this

Epidermal Growth Factor receptor (EGFR) regulates mechanical ventilation-induced lung injury in mice. / Bierman, Alexis; Yerrapureddy, Adi; Reddy, Narsa M.; Hassoun, Paul M; Reddy, Sekhar P.

In: Translational Research, Vol. 152, No. 6, 12.2008, p. 265-272.

Research output: Contribution to journalArticle

Bierman, Alexis ; Yerrapureddy, Adi ; Reddy, Narsa M. ; Hassoun, Paul M ; Reddy, Sekhar P. / Epidermal Growth Factor receptor (EGFR) regulates mechanical ventilation-induced lung injury in mice. In: Translational Research. 2008 ; Vol. 152, No. 6. pp. 265-272.
@article{02981a2a0cd0402d92a59810ea2615fd,
title = "Epidermal Growth Factor receptor (EGFR) regulates mechanical ventilation-induced lung injury in mice",
abstract = "Mechanical ventilation (MV) is used as therapy to support critically ill patients; however, the mechanisms by which MV induces lung injury and inflammation remain unclear. Epidermal growth factor receptor (EGFR)-mediated signaling plays a key role in various physiologic and pathologic processes, which include those modulated by mechanical and shear forces, in various cell types. We hypothesized that EGFR-activated signaling plays a key role in ventilator-induced lung injury and inflammation (VILI). To test this hypothesis, we assessed lung vascular and alveolar permeability as well as inflammation, which are cardinal features of VILI, in mice treated with the EGFR inhibitor AG1478. Inhibition of EGFR activity greatly diminished MV-induced lung alveolar permeability and neutrophil accumulation in the bronchoalveolar lavage (BAL) fluid, as compared with vehicle-treated controls. Similarly, AG1478 inhibition diminished lung vascular leak (as assessed by Evans blue extravasation), but it did not affect interstitial neutrophil accumulation. Inhibition of the EGFR pathway also blocked expression of genes induced by MV. However, intratracheal instillation of EGF alone failed to induce lung injury. Collectively, our findings suggest that EGFR-activated signaling is necessary but not sufficient to produce acute lung injury in mice.",
author = "Alexis Bierman and Adi Yerrapureddy and Reddy, {Narsa M.} and Hassoun, {Paul M} and Reddy, {Sekhar P.}",
year = "2008",
month = "12",
doi = "10.1016/j.trsl.2008.10.004",
language = "English (US)",
volume = "152",
pages = "265--272",
journal = "Translational Research",
issn = "1931-5244",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - Epidermal Growth Factor receptor (EGFR) regulates mechanical ventilation-induced lung injury in mice

AU - Bierman, Alexis

AU - Yerrapureddy, Adi

AU - Reddy, Narsa M.

AU - Hassoun, Paul M

AU - Reddy, Sekhar P.

PY - 2008/12

Y1 - 2008/12

N2 - Mechanical ventilation (MV) is used as therapy to support critically ill patients; however, the mechanisms by which MV induces lung injury and inflammation remain unclear. Epidermal growth factor receptor (EGFR)-mediated signaling plays a key role in various physiologic and pathologic processes, which include those modulated by mechanical and shear forces, in various cell types. We hypothesized that EGFR-activated signaling plays a key role in ventilator-induced lung injury and inflammation (VILI). To test this hypothesis, we assessed lung vascular and alveolar permeability as well as inflammation, which are cardinal features of VILI, in mice treated with the EGFR inhibitor AG1478. Inhibition of EGFR activity greatly diminished MV-induced lung alveolar permeability and neutrophil accumulation in the bronchoalveolar lavage (BAL) fluid, as compared with vehicle-treated controls. Similarly, AG1478 inhibition diminished lung vascular leak (as assessed by Evans blue extravasation), but it did not affect interstitial neutrophil accumulation. Inhibition of the EGFR pathway also blocked expression of genes induced by MV. However, intratracheal instillation of EGF alone failed to induce lung injury. Collectively, our findings suggest that EGFR-activated signaling is necessary but not sufficient to produce acute lung injury in mice.

AB - Mechanical ventilation (MV) is used as therapy to support critically ill patients; however, the mechanisms by which MV induces lung injury and inflammation remain unclear. Epidermal growth factor receptor (EGFR)-mediated signaling plays a key role in various physiologic and pathologic processes, which include those modulated by mechanical and shear forces, in various cell types. We hypothesized that EGFR-activated signaling plays a key role in ventilator-induced lung injury and inflammation (VILI). To test this hypothesis, we assessed lung vascular and alveolar permeability as well as inflammation, which are cardinal features of VILI, in mice treated with the EGFR inhibitor AG1478. Inhibition of EGFR activity greatly diminished MV-induced lung alveolar permeability and neutrophil accumulation in the bronchoalveolar lavage (BAL) fluid, as compared with vehicle-treated controls. Similarly, AG1478 inhibition diminished lung vascular leak (as assessed by Evans blue extravasation), but it did not affect interstitial neutrophil accumulation. Inhibition of the EGFR pathway also blocked expression of genes induced by MV. However, intratracheal instillation of EGF alone failed to induce lung injury. Collectively, our findings suggest that EGFR-activated signaling is necessary but not sufficient to produce acute lung injury in mice.

UR - http://www.scopus.com/inward/record.url?scp=57649100799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57649100799&partnerID=8YFLogxK

U2 - 10.1016/j.trsl.2008.10.004

DO - 10.1016/j.trsl.2008.10.004

M3 - Article

C2 - 19059161

AN - SCOPUS:57649100799

VL - 152

SP - 265

EP - 272

JO - Translational Research

JF - Translational Research

SN - 1931-5244

IS - 6

ER -