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Alternatively Activated Macrophages and Airway DiseaseMacrophages and Airway Disease

Derek E. Byers, MD, PhD; Michael J. Holtzman, MD, FCCP
Author and Funding Information

From the Department of Pulmonary and Critical Care Medicine, Department of Medicine, and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO.

Correspondence to: Michael J. Holtzman, MD, FCCP, Washington University School of Medicine, Campus Box 8052, 660 S Euclid Ave, St. Louis, MO 63110; e-mail: holtzmanm@wustl.edu


Funding/Support: The research reviewed here was supported by grants from the National Institutes of Health (National Heart, Lung, and Blood Institute and National Institute of Allergy and Infectious Diseases) and the Martin Schaeffer Fund.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;140(3):768-774. doi:10.1378/chest.10-2132
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Macrophages are the most abundant immune cell population in normal lung tissue and serve critical roles in innate and adaptive immune responses as well as the development of inflammatory airway disease. Studies in a mouse model of chronic obstructive lung disease and translational studies of humans with asthma and COPD have shown that a special subset of macrophages is required for disease progression. This subset is activated by an alternative pathway that depends on production of IL-4 and IL-13, in contrast to the classic pathway driven by interferon-γ. Recent and unexpected results indicate that alternatively activated macrophages (AAMs) can also become a major source of IL-13 production and, thereby, drive the increased mucus production and airway hyperreactivity that is characteristic of airway disease. Although the normal and abnormal functions of AAMs are still being defined, it is already apparent that markers of this immune cell subset can be useful to guide stratification and treatment of patients with chronic airway diseases. Here, we review basic and clinical research studies that highlight the importance of AAMs in the pathogenesis of asthma, COPD, and other chronic airway diseases.

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