Characterisation of the proximal airway squamous metaplasia induced by chronic tobacco smoke exposure in spontaneously hypertensive rats

Sarah J. Bolton, Kate Pinnion, Victor Oreffo, Martyn Foster, Kent E Pinkerton

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Continuous exposure to tobacco smoke (TS) is a key cause of chronic obstructive pulmonary disease (COPD), a complex multifactorial disease that is difficult to model in rodents. The spontaneously hypertensive (SH) rat exhibits several COPD-associated co-morbidities such as hypertension and increased coagulation. We have investigated whether SH rats are a more appropriate animal paradigm of COPD.Methods: SH rats were exposed to TS for 6 hours/day, 3 days/week for 14 weeks, and the lung tissues examined by immunohistochemistry.Results: TS induced a CK13-positive squamous metaplasia in proximal airways, which also stained for Ki67 and p63. We hypothesise that this lesion arises by basal cell proliferation, which differentiates to a squamous cell phenotype. Differences in staining profiles for the functional markers CC10 and surfactant D, but not phospho-p38, indicated loss of ability to function appropriately as secretory cells. Within the parenchyma, there were also differences in the staining profiles for CC10 and surfactant D, indicating a possible attempt to compensate for losses in proximal airways. In human COPD sections, areas of CK13-positive squamous metaplasia showed sporadic p63 staining, suggesting that unlike the rat, this is not a basal cell-driven lesion.Conclusion: This study demonstrates that although proximal airway metaplasia in rat and human are both CK13+ and therefore squamous, they potentially arise by different mechanisms.

Original languageEnglish (US)
Article number118
JournalRespiratory Research
Volume10
DOIs
StatePublished - Nov 24 2009

Fingerprint

Metaplasia
Inbred SHR Rats
Smoke
Chronic Obstructive Pulmonary Disease
Tobacco
Staining and Labeling
Surface-Active Agents
Rodentia
Epithelial Cells
Immunohistochemistry
Cell Proliferation
Hypertension
Morbidity
Phenotype
Lung

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Characterisation of the proximal airway squamous metaplasia induced by chronic tobacco smoke exposure in spontaneously hypertensive rats. / Bolton, Sarah J.; Pinnion, Kate; Oreffo, Victor; Foster, Martyn; Pinkerton, Kent E.

In: Respiratory Research, Vol. 10, 118, 24.11.2009.

Research output: Contribution to journalArticle

@article{ccf0dbc116c34fd0a879083c4206cdd8,
title = "Characterisation of the proximal airway squamous metaplasia induced by chronic tobacco smoke exposure in spontaneously hypertensive rats",
abstract = "Background: Continuous exposure to tobacco smoke (TS) is a key cause of chronic obstructive pulmonary disease (COPD), a complex multifactorial disease that is difficult to model in rodents. The spontaneously hypertensive (SH) rat exhibits several COPD-associated co-morbidities such as hypertension and increased coagulation. We have investigated whether SH rats are a more appropriate animal paradigm of COPD.Methods: SH rats were exposed to TS for 6 hours/day, 3 days/week for 14 weeks, and the lung tissues examined by immunohistochemistry.Results: TS induced a CK13-positive squamous metaplasia in proximal airways, which also stained for Ki67 and p63. We hypothesise that this lesion arises by basal cell proliferation, which differentiates to a squamous cell phenotype. Differences in staining profiles for the functional markers CC10 and surfactant D, but not phospho-p38, indicated loss of ability to function appropriately as secretory cells. Within the parenchyma, there were also differences in the staining profiles for CC10 and surfactant D, indicating a possible attempt to compensate for losses in proximal airways. In human COPD sections, areas of CK13-positive squamous metaplasia showed sporadic p63 staining, suggesting that unlike the rat, this is not a basal cell-driven lesion.Conclusion: This study demonstrates that although proximal airway metaplasia in rat and human are both CK13+ and therefore squamous, they potentially arise by different mechanisms.",
author = "Bolton, {Sarah J.} and Kate Pinnion and Victor Oreffo and Martyn Foster and Pinkerton, {Kent E}",
year = "2009",
month = "11",
day = "24",
doi = "10.1186/1465-9921-10-118",
language = "English (US)",
volume = "10",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Characterisation of the proximal airway squamous metaplasia induced by chronic tobacco smoke exposure in spontaneously hypertensive rats

AU - Bolton, Sarah J.

AU - Pinnion, Kate

AU - Oreffo, Victor

AU - Foster, Martyn

AU - Pinkerton, Kent E

PY - 2009/11/24

Y1 - 2009/11/24

N2 - Background: Continuous exposure to tobacco smoke (TS) is a key cause of chronic obstructive pulmonary disease (COPD), a complex multifactorial disease that is difficult to model in rodents. The spontaneously hypertensive (SH) rat exhibits several COPD-associated co-morbidities such as hypertension and increased coagulation. We have investigated whether SH rats are a more appropriate animal paradigm of COPD.Methods: SH rats were exposed to TS for 6 hours/day, 3 days/week for 14 weeks, and the lung tissues examined by immunohistochemistry.Results: TS induced a CK13-positive squamous metaplasia in proximal airways, which also stained for Ki67 and p63. We hypothesise that this lesion arises by basal cell proliferation, which differentiates to a squamous cell phenotype. Differences in staining profiles for the functional markers CC10 and surfactant D, but not phospho-p38, indicated loss of ability to function appropriately as secretory cells. Within the parenchyma, there were also differences in the staining profiles for CC10 and surfactant D, indicating a possible attempt to compensate for losses in proximal airways. In human COPD sections, areas of CK13-positive squamous metaplasia showed sporadic p63 staining, suggesting that unlike the rat, this is not a basal cell-driven lesion.Conclusion: This study demonstrates that although proximal airway metaplasia in rat and human are both CK13+ and therefore squamous, they potentially arise by different mechanisms.

AB - Background: Continuous exposure to tobacco smoke (TS) is a key cause of chronic obstructive pulmonary disease (COPD), a complex multifactorial disease that is difficult to model in rodents. The spontaneously hypertensive (SH) rat exhibits several COPD-associated co-morbidities such as hypertension and increased coagulation. We have investigated whether SH rats are a more appropriate animal paradigm of COPD.Methods: SH rats were exposed to TS for 6 hours/day, 3 days/week for 14 weeks, and the lung tissues examined by immunohistochemistry.Results: TS induced a CK13-positive squamous metaplasia in proximal airways, which also stained for Ki67 and p63. We hypothesise that this lesion arises by basal cell proliferation, which differentiates to a squamous cell phenotype. Differences in staining profiles for the functional markers CC10 and surfactant D, but not phospho-p38, indicated loss of ability to function appropriately as secretory cells. Within the parenchyma, there were also differences in the staining profiles for CC10 and surfactant D, indicating a possible attempt to compensate for losses in proximal airways. In human COPD sections, areas of CK13-positive squamous metaplasia showed sporadic p63 staining, suggesting that unlike the rat, this is not a basal cell-driven lesion.Conclusion: This study demonstrates that although proximal airway metaplasia in rat and human are both CK13+ and therefore squamous, they potentially arise by different mechanisms.

UR - http://www.scopus.com/inward/record.url?scp=73949135486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73949135486&partnerID=8YFLogxK

U2 - 10.1186/1465-9921-10-118

DO - 10.1186/1465-9921-10-118

M3 - Article

C2 - 19930705

AN - SCOPUS:73949135486

VL - 10

JO - Respiratory Research

JF - Respiratory Research

SN - 1465-9921

M1 - 118

ER -