Jeffrey D. Laskin

Chapter 32 – Pulmonary Macrophages

Macrophages are major sentinels of the lung, functioning as the first line of defense against inhaled pathogens. They are located in the alveoli, interstitium, airways, pleura, and in some species, the vasculature. Displaying unique phenotypes and functions, these pulmonary macrophage subpopulations work together to maintain homeostasis in the lung. They also participate in inflammatory responses to tissue injury and infection. Under normal conditions, the activity of pulmonary macrophages is suppressed in order to limit over reaction to innocuous stimuli. Noxious agents and pathogens can readily overcome this negative regulation. This leads to macrophage activation and the release of proinflammatory/cytotoxic and mitogenic mediators aimed at protecting the host and restoring homeostasis. However, when release of these mediators by activated macrophages is excessive or uncontrolled, they may in fact contribute to disease pathogenesis. Macrophage activation and functioning are regulated by diverse receptors that are engaged by cytokines and inflammatory mediators in the tissue. Thus, as the microenvironment changes, the phenotype and function of these cells also changes. Evidence suggests that activation of macrophages is a dynamic process whereby the same cells can sequentially participate in multiple host defense activities. This remarkable plasticity of macrophages enables them to adapt to a changing environment and is critical for effective host defense.