help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on September 15, 2005, doi:10.1164/rccm.200505-686OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 11, December 2005, 1383-1392

A more recent version of this article appeared on December 1, 2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200505-686OCv1
172/11/1383    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Woodruff, P. G
Right arrow Articles by Erle, D. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Woodruff, P. G
Right arrow Articles by Erle, D. J

Submitted on May 1, 2005
Accepted on September 15, 2005

A Distinctive Alveolar Macrophage Activation State Induced by Cigarette Smoking

Prescott G Woodruff1, Laura L Koth2*, Yee Hwa Yang3, Madeleine W Rodriguez4, Silvio Favoreto5, Gregory M Dolganov1, Agnes C Paquet4, and David J Erle6

1 Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA, 2 Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, Lung Biology Center, San Francisco, CA, USA, 3 Department of Medicine, University of California, San Francisco, Lung Biology Center, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA, 4 Department of Medicine, University of California, San Francisco, Lung Biology Center, San Francisco, CA, USA, 5 Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA, USA, 6 Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, Lung Biology Center, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: Laura.Koth{at}ucsf.edu.

Rationale: Macrophages are thought to play a central role in emphysema based largely on data from mouse models. However, the relevance of these models to smoking-related lung disease in humans is uncertain. Objectives: We sought to comprehensively characterize the effects of smoking on gene expression in human alveolar macrophages and to compare these with effects seen in transgenic mouse models of emphysema. Methods: We used DNA microarrays with genome-wide coverage to analyze alveolar macrophages from 15 smokers, 15 non-smokers, and 15 asthmatics (disease control). Selected gene expression changes were validated by PCR and ELISA. Expression changes were compared with those identified by microarray analysis of IL-13 overexpressing and integrin {beta}6-deficient mice, which both develop emphysema. Measurements and Main Results: All 15 smokers shared a common pattern of macrophage gene expression that distinguished them from non-smokers, a finding not observed in asthmatics. We identified 110 genes as differentially expressed in smokers despite using conservative statistical methods. MMP-12, a proteinase which plays a critical role in mouse models, was the third most highly induced gene in smokers (9-fold, p<0.0001). However, most changes in smokers were not reflected in mouse models. One such finding was increased osteopontin expression in smokers (4-fold, p=0.006), which was confirmed at the protein level and correlated with the degree of airway obstruction. Conclusions: Smoking induces a remarkably consistent and distinctive pattern of alveolar macrophage activation. These studies identify aspects of mouse models that are directly relevant to human smokers and also reveal novel potential mediators of smoking-related diseases.
Key words: Gene Expression Profiling; Pulmonary Emphysema; Matrix Metalloproteinases; Osteopontin.




This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
P. G. Woodruff, B. Modrek, D. F. Choy, G. Jia, A. R. Abbas, A. Ellwanger, J. R. Arron, L. L. Koth, and J. V. Fahy
T-helper Type 2-driven Inflammation Defines Major Subphenotypes of Asthma
Am. J. Respir. Crit. Care Med., September 1, 2009; 180(5): 388 - 395.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Shaykhiev, A. Krause, J. Salit, Y. Strulovici-Barel, B.-G. Harvey, T. P. O'Connor, and R. G. Crystal
Smoking-Dependent Reprogramming of Alveolar Macrophage Polarization: Implication for Pathogenesis of Chronic Obstructive Pulmonary Disease
J. Immunol., August 15, 2009; 183(4): 2867 - 2883.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
A. Prasse, M. Stahl, G. Schulz, G. Kayser, L. Wang, K. Ask, J. Yalcintepe, A. Kirschbaum, E. Bargagli, G. Zissel, et al.
Essential Role of Osteopontin in Smoking-Related Interstitial Lung Diseases
Am. J. Pathol., May 1, 2009; 174(5): 1683 - 1691.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
E. J. Lee, K. H. In, J. H. Kim, S. Y. Lee, C. Shin, J. J. Shim, K. H. Kang, S. H. Yoo, C. H. Kim, H.-K. Kim, et al.
Proteomic Analysis in Lung Tissue of Smokers and COPD Patients
Chest, February 1, 2009; 135(2): 344 - 352.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
D Goven, A Boutten, V Lecon-Malas, J Marchal-Somme, N Amara, B Crestani, M Fournier, G Leseche, P Soler, J Boczkowski, et al.
Altered Nrf2/Keap1-Bach1 equilibrium in pulmonary emphysema
Thorax, October 1, 2008; 63(10): 916 - 924.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
K. F. Chung and I. M. Adcock
Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction
Eur. Respir. J., June 1, 2008; 31(6): 1334 - 1356.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. J. Cornish, B. J. Hurtgen, K. McInnerney, N. L. Burritt, R. M. Taylor, J. N. Jarvis, S. Y. Wang, and J. B. Burritt
Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Independent Resistance to Aspergillus fumigatus in Alveolar Macrophages
J. Immunol., May 15, 2008; 180(10): 6854 - 6867.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Churg, M. Cosio, and J. L. Wright
Mechanisms of cigarette smoke-induced COPD: insights from animal models
Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L612 - L631.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. C. Lewis, J. Y. H. Yang, X. Huang, S. K. Banerjee, M. R. Blackburn, P. Baluk, D. M. McDonald, T. S. Blackwell, V. Nagabhushanam, W. Peters, et al.
Disease-Specific Gene Expression Profiling in Multiple Models of Lung Disease
Am. J. Respir. Crit. Care Med., February 15, 2008; 177(4): 376 - 387.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
G. S. Horan, S. Wood, V. Ona, D. J. Li, M. E. Lukashev, P. H. Weinreb, K. J. Simon, K. Hahm, N. E. Allaire, N. J. Rinaldi, et al.
Partial Inhibition of Integrin {alpha}v 6 Prevents Pulmonary Fibrosis without Exacerbating Inflammation
Am. J. Respir. Crit. Care Med., January 1, 2008; 177(1): 56 - 65.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
L. L. Koth, B. Alex, S. Hawgood, M. A. Nead, D. Sheppard, D. J. Erle, and D. G. Morris
Integrin beta6 Mediates Phospholipid and Collectin Homeostasis by Activation of Latent TGF-beta1
Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 651 - 659.
[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
 ThoraxHome page
A. Churg, R. Wang, X. Wang, P.-O. Onnervik, K. Thim, and J. L Wright
Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs
Thorax, August 1, 2007; 62(8): 706 - 713.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
M. M. Wurfel
Microarray-based Analysis of Ventilator-induced Lung Injury
Proceedings of the ATS, January 1, 2007; 4(1): 77 - 84.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
D. G. Morris and D. Sheppard
Pulmonary Emphysema: When More is Less.
Physiology, December 1, 2006; 21(6): 396 - 403.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S. Gebel, B. Gerstmayer, P. Kuhl, J. Borlak, K. Meurrens, and T. Muller
The Kinetics of Transcriptomic Changes Induced by Cigarette Smoke in Rat Lungs Reveals a Specific Program of Defense, Inflammation, and Circadian Clock Gene Expression
Toxicol. Sci., October 1, 2006; 93(2): 422 - 431.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
L. M. Fabbri, F. Luppi, B. Beghe, and K. F. Rabe
Update in chronic obstructive pulmonary disease 2005.
Am. J. Respir. Crit. Care Med., May 15, 2006; 173(10): 1056 - 1065.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2005 American Thoracic Society 		  ATS 2008 State of the Art Course