This chapter describes the macrophage and lymphocyte populations present in the lung, in both the absence and presence of inflammatory stimuli. This distinction may be artificial, as the lung actively interfaces with the aero-environment and thus is constantly exposed to stimuli. While we describe the phenotypes themselves, other chapters cover the inflammatory processes and migratory stimuli that change the inflammatory cell complexion in the lung in disease states. Of greatest importance is to note that there is marked heterogeneity of cell surface markers, secretory products, and macrophage and lymphocyte functions in the lung that, together, represent the overall responses to stimuli and pathogens and the resolution of inflammation. We defer discussion of disease states to other chapters, only peripherally referring to unique roles of specific macrophage or lymphocyte subtypes when important to understanding the phenotypes. Our approach is to divide the chapter into descriptions of leukocyte subtypes of the innate (macrophages and lymphocytes) and adaptive (lymphocytes) immune systems, recognizing that there are many other ways to classify the inflammatory cell populations in the lung. Innate and adaptive immunity are described in detail in other chapters.
LUNG LEUKOCYTES IN THE INNATE IMMUNE SYSTEM
A variety of macrophages and lymphocytes are found in the lung and are discussed below.
Macrophages are large mononuclear cells with phagocytic capability that are found throughout the lung airspaces and parenchyma at baseline and during inflammation.1 These cells are key components of innate immune responses in the lung and manifest diverse functions that are associated with cell location, cell stimuli, and cellular origin. Their functions include: (1) phagocytic clearance of inhaled particles, pathogens, and apoptotic cells; (2) immunologic surveillance, raising an immunologic alarm in the presence of pathogenic but not innocuous stimuli; (3) immune regulation by interfacing with other members of innate and adaptive immune responses; and (4) promoting resolution and repair pathways after an injurious insult. No single macrophage effects all these disparate roles. Rather, macrophage populations are diverse and dynamic; they originate from multiple cell types and retain a remarkable degree of functional plasticity over their potentially long life.2 Because of this diversity, many classification schemas have been developed to categorize macrophages, based on surface markers, location, and function.3
In recent years, especially with the emergence of single cell-based analytic techniques, it has become clear that many of these systems inadequately describe the full breadth of macrophage heterogeneity. Here, we describe lung macrophage population based on primary location—airspace/alveolar vs. interstitial/tissue-resident macrophages—and describe the current understanding of subcategories in each of these regions. This is a rapidly evolving field, and our understanding will likely be further refined in the future.
Alveolar macrophages (AMs) are defined primarily by their location in the alveolar space (Fig. 20-1) and their accessibility via bronchoalveolar lavage. Their ...