Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics

Vasanthi R. Sunil, Kinal N. Vayas, Christopher B. Massa, Andrew J. Gow, Jeffrey D. Laskin, Debra L. Laskin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase- 1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.

Original languageEnglish
Pages (from-to)309-319
Number of pages11
JournalToxicological Sciences
Volume133
Issue number2
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

Fingerprint

Oxidative stress
Ozone
Mechanics
Oxidative Stress
Epithelium
Lung
Wounds and Injuries
Methacholine Chloride
Uteroglobin
Apoptosis
Galectin 3
Lung Compliance
Arginase
Bronchiolitis
Heme Oxygenase-1
Caspase 9
Cilia
Tidal Volume
Autophagy
Bronchoalveolar Lavage

Keywords

  • Bronchiole
  • Epithelium
  • Oxidative stress
  • Ozone
  • Pulmonary mechanics

ASJC Scopus subject areas

  • Toxicology

Cite this

Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics. / Sunil, Vasanthi R.; Vayas, Kinal N.; Massa, Christopher B.; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

In: Toxicological Sciences, Vol. 133, No. 2, 06.2013, p. 309-319.

Research output: Contribution to journalArticle

Sunil, Vasanthi R. ; Vayas, Kinal N. ; Massa, Christopher B. ; Gow, Andrew J. ; Laskin, Jeffrey D. ; Laskin, Debra L. / Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics. In: Toxicological Sciences. 2013 ; Vol. 133, No. 2. pp. 309-319.
@article{78dee61ae76b4281906a438e35f1b9c2,
title = "Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics",
abstract = "In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase- 1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.",
keywords = "Bronchiole, Epithelium, Oxidative stress, Ozone, Pulmonary mechanics",
author = "Sunil, {Vasanthi R.} and Vayas, {Kinal N.} and Massa, {Christopher B.} and Gow, {Andrew J.} and Laskin, {Jeffrey D.} and Laskin, {Debra L.}",
year = "2013",
month = "6",
doi = "10.1093/toxsci/kft071",
language = "English",
volume = "133",
pages = "309--319",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics

AU - Sunil, Vasanthi R.

AU - Vayas, Kinal N.

AU - Massa, Christopher B.

AU - Gow, Andrew J.

AU - Laskin, Jeffrey D.

AU - Laskin, Debra L.

PY - 2013/6

Y1 - 2013/6

N2 - In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase- 1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.

AB - In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase- 1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.

KW - Bronchiole

KW - Epithelium

KW - Oxidative stress

KW - Ozone

KW - Pulmonary mechanics

UR - http://www.scopus.com/inward/record.url?scp=84878494967&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878494967&partnerID=8YFLogxK

U2 - 10.1093/toxsci/kft071

DO - 10.1093/toxsci/kft071

M3 - Article

VL - 133

SP - 309

EP - 319

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -