Update on the role of alternatively activated macrophages in asthma

Abstract

Lung macrophages link innate and adaptive immune responses during allergic airway inflammatory responses. Alveolar macrophages (AMs) and interstitial macrophages are two different phenotypes that differentially exert immunological function under physiological and pathological conditions. Exposure to pathogen induces polarization of AM cells into classically activated macrophages (M1 cells) and alternatively activated macrophages (M2 cells). M1 cells dominantly express proinflammatory cytokines such as TNF-α and IL-1 β and induce lung inflammation and tissue damage. M2 cells are further divided into M2a and M2c subsets. M2a cells dominantly produce allergic cytokines IL-4 and IL-13, but M2c cells dominantly produce anti-inflammatory cytokine IL-10. M2a and M2c cells are differently involved in initiation, inflammation resolution, and tissue remodeling in the different stages of asthma. Microenvironment dynamically influences polarization of AM cells. Cytokines, chemokines, and immune-regulatory cells interplay and affect the balance between the polarization of M1 and M2 cells, subsequently influencing disease progression. Thus, modulation of AM phenotypes through molecular intervention has therapeutic potential in the treatment of asthma and other allergic inflammatory diseases. This review updated recent advances in polarization and functional specialization of these macrophage subtypes with emphasis on modulation of polarization of M2 cells in asthma of human subjects and animal models.

Keywords:

• asthma
• macrophage polarization
• alternatively activated macrophages
• M2 cells
• cytokines

Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China to LZ (81270137) and a research grant from Zhongshan Hospital, Fudan University, People’s Republic of China, to ZLJ (A654116001). The authors thank Kelly Yiting Jiang from Cornell University for her scientific editing assistance in the preparation of this manuscript.

Disclosure

The authors report no conflicts of interest in this work. None of the authors affiliated with this manuscript have any commercial associations that might pose a conflict of interest. The authors alone are responsible for the content and writing of the article.