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Interstitial and Peribronchial Macrophages in Chronic Obstructive Pulmonary Disease Display an Alternatively Activated Phenotype

University of Colorado Health Sciences Center; and National Jewish Medical and Research Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Marc A. Voelkel, M.D., Pulmonary Division, UCHSC, Box C272, 4200 East Ninth Avenue, Denver, CO 80262. E-mail: marc.voelkel{at}uchsc.edu

Chronic obstructive pulmonary disease (COPD) is a large and growing health care issue with a high degree of morbidity and mortality. Cigarette smoking is attributed to be a major factor in development of COPD. Macrophages may play a critical role in the pathophysiology of COPD where they are localized to sites of alveolar wall destruction in emphysema and airway remodeling. Recent studies have implicated the Th2 cytokines interleukin (IL)-4 and IL-13 in airway hyperresponsiveness and COPD. Macrophages stimulated with IL-4 and/or IL-13 are classified as alternatively activated macrophages in contrast to IFN-–stimulated classically activated macrophages. In COPD, there is often a combined phenotype of emphysema and airway hyperresponsiveness, with small airway peribronchial fibrosis. Therefore, the purpose of this study was to explore the hypothesis that macrophages in the lung interstitium and airways of patients with COPD display an alternatively activated phenotype, whereas those in the alveolar spaces display the classically activated phenotype. Serial lung sections of human patients with COPD and normal control subjects were immunohistochemically stained for CD68 (a macrophage marker), arginase I and chitinase-like 3 protein (YMV2) (markers of alternatively activated macrophages), and inducible nitric oxide synthase (iNOS; classically activated macrophage marker). In COPD, lung alveolar macrophages stained positive for both CD68 and iNOS, whereas interstitial and peribronchial CD68 macrophages stained positive for both arginase I and YMV2. Normal lung sections had minimal alveolar and interstitial macrophages, with no iNOS-, YMV2, or arginase I–positive cells. Thus, in COPD, lung interstitial and peribronchial macrophages display an alternatively activated phenotype in contrast to alveolar macrophages, which display a classically activated phenotype.

FOOTNOTES

Conflict of Interest Statement: M.A.V. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.M.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.W.W. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.W.H.R. has been reimbursed by Novartis for attending a workshop on interstitial pulmonary fibrosis (IPF).

(Received in original form March 17, 2006; accepted in final form March 28, 2006)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Voelkel, M. A. Articles by Riches, D. W. H. Search for Related Content PubMed Articles by Voelkel, M. A. Articles by Riches, D. W. H.