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1 Respiratory Disease Area, Novartis Institute of Biomedical Research, Horsham, United Kingdom
* To whom correspondence should be addressed. E-mail: Christopher.Stevenson{at}pharma.novartis.com.
Repetitive, acute inflammatory insults elicited by cigarette smoke 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 exposure to cigarette smoke (CS). 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 2 exposures to CS (15 h apart) elicited a robust inflammatory/mucus hypersecretory
phenotype that was used to investigate mechanisms driving this response. CINCs 1-3, the rat GRO-
family homologues, 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, SB332235, effectively inhibited CS-induced neutrophilia
in a dose-dependent manner, supporting this conclusion. This modelling of the response of the rat airways to acute CS exposure indicates: 1.) as few as 2 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 contributes to the development of chronic disease.
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 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]
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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]
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