Lung Macrophages in Health and Disease

Macrophage Functional Plasticity: Implications for Cancer Progression and Therapy

Author(s): Robert D. Stout and Jill Suttles

Pp: 37-51 (15)

DOI: 10.2174/978160805020810901010037

* (Excluding Mailing and Handling)


Macrophages contribute significantly to the development and progression of chronic lung diseases and lung cancer [1-3]. Persistent stimulation by airborne irritants promotes recruitment of blood monocytes into the lung and also disrupts homeostatic control of interstitial and alveolar macrophages [1-3]. Both resident and recruited macrophages contribute to increased oxidative stress and to the production of inflammatory, fibrotic, and angiogenic cytokines that promote the hyperplasia and fibrosis of Chronic Obstructive Pulmonary Disease (COPD) as well as the growth and metastasis of lung tumors [1,2,4-13]. These studies raise several broad questions. Why do the functions of resident macrophages change? Alveolar macrophages function predominantly in particle clearance and are considered to have “restrained” inflammatory and cytotoxic activity [14,15]. The functional activities displayed by macrophages in COPD and lung cancer are very diverse, including production of both inflammatory and anti-inflammatory cytokines and expression of both tissue destructive (e.g., oxidants, metalloproteinases) and tissue reparative (e.g., angiogenic and growth factors) activities [1,2,4,5,7,8,13,16]. How are they converted to produce inflammatory mediators and matrix destructive proteinases [2,11-13]? How are these apparently antagonistic activities expressed simultaneously in diseased tissue? The following sections will provide insight into the answers to these questions, emphasizing the importance of tissue homeostatic mechanisms, microenvironmental influence on macrophage function, and macrophage functional plasticity. Macrophage biology will be discussed in the context of lung cancer, but given the similarities between macrophage contributions to cancer and COPD progression, the potential for therapeutic targeting of macrophage functional plasticity and tissue: macrophage interactions should apply to both diseases.

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