AJP - Lung AJP: Advances in Physiology Education
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 288: L514-L522, 2005. First published October 29, 2004; doi:10.1152/ajplung.00317.2004
1040-0605/05 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/3/L514    most recent
00317.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (16)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stevenson, C. S.
Right arrow Articles by Danahay, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stevenson, C. S.
Right arrow Articles by Danahay, H.

Characterization of cigarette smoke-induced inflammatory and mucus hypersecretory changes in rat lung and the role of CXCR2 ligands in mediating this effect

Christopher S. Stevenson, Kevin Coote, Ruth Webster, Helinor Johnston, Hazel C. Atherton, Andrew Nicholls, June Giddings, Rosemary Sugar, Alan Jackson, Neil J. Press, Zarin Brown, Keith Butler, and Henry Danahay

Novartis Institute of Biomedical Research, Respiratory Disease Area, Horsham, West Sussex, United Kingdom

Submitted 23 August 2004 ; accepted in final form 25 October 2004

Repetitive, acute inflammatory insults elicited by cigarette smoke (CS) contribute to the development of chronic obstructive pulmonary disease (COPD), a disorder associated with lung inflammation and mucus hypersecretion. Presently, there is a poor understanding of the acute inflammatory mechanisms involved in this process. The aims of this study were to develop an acute model to investigate temporal inflammatory changes occurring after CS exposure. Rats were exposed to whole body CS (once daily) generated from filtered research cigarettes. Initial studies indicated the generation of a neutrophilic/mucus hypersecreting lung phenotype in <4 days. Subsequent studies demonstrated that just two exposures to CS (15 h apart) elicited a robust inflammatory/mucus hypersecretory phenotype that was used to investigate mechanisms driving this response. Cytokine-induced neutrophil chemoattractants (CINCs) 1–3, the rat growth-related oncogene-{alpha} family homologs, and IL-1{beta} demonstrated time-dependent increases in lung tissue or lavage fluid over the 24-h period following CS exposure. The temporal changes in the neutrophil chemokines, CINCs 1–3, mirrored increases in neutrophil infiltration, indicative of a role in neutrophil migration. In addition, a specific CXCR2 antagonist, SB-332235, effectively inhibited CS-induced neutrophilia in a dose-dependent manner, supporting this conclusion. This modeling of the response of the rat airways to acute CS exposure indicates 1) as few as two exposures to CS will induce a phenotype with similarities to COPD and 2) a novel role for CINCs in the generation of this response. These observations represent a paradigm for the study of acute, repetitive lung insults that contribute to the development of chronic disease.

chronic obstructive pulmonary disease; neutrophils; smoking; cytokine-induced neutrophil chemoattractant


Address for reprint requests and other correspondence: C. S. Stevenson, Novartis Respiratory Research Centre, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, UK (E-mail: Christopher.Stevenson{at}pharma.novartis.com)




This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
T. R. Johnson, M. E. Rothenberg, and B. S. Graham
Pulmonary eosinophilia requires interleukin-5, eotaxin-1, and CD4+ T cells in mice immunized with respiratory syncytial virus G glycoprotein
J. Leukoc. Biol., September 1, 2008; 84(3): 748 - 759.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. S. Stevenson, C. Docx, R. Webster, C. Battram, D. Hynx, J. Giddings, P. R. Cooper, P. Chakravarty, I. Rahman, J. A. Marwick, et al.
Comprehensive gene expression profiling of rat lung reveals distinct acute and chronic responses to cigarette smoke inhalation
Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1183 - L1193.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
J. L. Curtis, C. M. Freeman, and J. C. Hogg
The Immunopathogenesis of Chronic Obstructive Pulmonary Disease: Insights from Recent Research
Proceedings of the ATS, October 1, 2007; 4(7): 512 - 521.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
O. Bonneau, D. Wyss, S. Ferretti, C. Blaydon, C. S. Stevenson, and A. Trifilieff
Effect of adenosine A2A receptor activation in murine models of respiratory disorders
Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L1036 - L1043.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2005 by the American Physiological Society.