cells in the airway. The discussion below of the response to inhaled protein first deals with the role of macrophages and T and B cells and then describes mast cells, eosinophils, and neutrophils, other cells that are significant in airway host defense.
In terms of number and presumably function, the alveolar and airway macrophages are the predominant airway inflammatory and immune effector cells. Airway macrophages are derived from precursor blood monocytes that migrate to the airways and differentiate there (Unanue and Cerottini, 1989). (The precursors of blood monocytes are monoblasts and promonocytes, which are found in bone marrow.) There are other cells in body tissue that are similar to airway and/or alveolar macrophages in distribution and differentiation—for example, Kupffer cells in the liver and osteoclasts of bone.
The function of macrophages is to provide nonspecific as well as specific host defense in various tissues; these tissue macrophages can be resting or activated, depending on local conditions. The ability of macrophages to "process" extracellular proteins, including inhaled proteins taken from ambient inspired air and leached from particles, makes them primary airway defenders; they not only eliminate inhaled proteins but also act as allergen-presenting and allergen-processing cells (Unanue and Cerottini, 1989). In addition, macrophages secrete diverse bioactive molecules that influence the physiology of many tissues; in the upper and lower airways they are critical to physiologic function. The nature of these proteins and of other host defense factors involved in the generation of responses by macrophages will be covered in more detail elsewhere in this chapter; macrophages are important in the maintenance of airway tissue.
The antigen-presenting cell (APC) is involved in immune and inflammatory reactions in the airway. Antigen presentation is mediated by the expression of specific proteins on the surface of the airway macrophage, which functions in the actual presentation and recognition of protein allergens and other APC antigens—by helper T cells in particular. The response to both inhaled and soluble proteins clearly depends on the CD4+ subtype of helper T cells (see the discussion below); thus, the role of the class II major histocompatibility complex (MHC) macrophages in presenting protein fragments to these T cells is critical (Unanue and Cerottini, 1989).