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.
