| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
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-
family homologs, and IL-1
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
This article has been cited by other articles:
|
|
 |
|
  A. Morris, G. Kinnear, W.-Y. H. Wan, D. Wyss, P. Bahra, and C. S. Stevenson Comparison of Cigarette Smoke-Induced Acute Inflammation in Multiple Strains of Mice and the Effect of a Matrix Metalloproteinase Inhibitor on These Responses J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 851 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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 |
