Inflammatory Cells of the Lung: Macrophages

The lung is an immunosuppressed organ, where reactions to inhaled foreign bodies are highly regulated. Macrophages play a key role in the pulmonary regulatory process as a major immune constituent of the alveolar, as well as interstitial, spaces. The macrophage is an important component of the innate immune system that plays a strong regulatory role as a vital link with adaptive immunity. This chapter provides an overview of the lung macrophage, its role in the regulation of lung immunity, and its response to toxic exposures and consequences to the host. Due to its important functions and location in the lungs, the macrophage is a critical target for xenobiotic-mediated lung injury. Xenobiotic agents have been implicated in various forms of lung injury from inducing immunosuppression to chronic inflammation through effects on the alveolar macrophage. In addition, subpopulations of macrophages have been described where unique phenotypes are the result of their mechanism of activation. The first portion of this chapter will describe the normal structure and functions of macrophage populations in the lung and the second portion will address macrophage responses to xenobiotic exposures. Plasticity of macrophage phenotypes may be central in regulating the fine balance required for normal lung physiology. To this end, this chapter describes the role of pulmonary macrophages with respect to environmental exposures. The functions and activities of macrophage subpopulations will be discussed in relation to alterations of those functions following environmental exposures. Although a great deal of information has been obtained, more questions remain. There are still undiscovered cytokines and even responses of the alveolar macrophage, as well as mechanisms of xenobiotic action that will alter our thinking in the future.