Phagocytes and the Lung

Activation of lung phagocytes, whether involving residential or recruited phagocytic cells (macrophages, monocytes, neutrophils), results in a series of products important for development of inflammatory injury of the lung. An understanding of the mechanisms of cell activation as well as how products of these activated cells interact with cellular and non-cellular targets to bring about tissue damage is important for the ultimate use of blocking interventions in the treatment of human inflammatory diseases. In these considerations, we will discuss cytokine products of activated macrophages, including pro-inflammatory cytokines, anti-inflammatory cytokines, oxidants, and proteinases (TABLE 1). All of the information to be presented in this paper derives from the study of an animal model of acute lung injury induced by intrapulmonary deposition of IgG immune complexes. This deposition results in a complement-dependent activation of lung macrophages, recruitment of large numbers of neutrophils, and ultimate damage of lung cells and matrix as a result of numerous products from activated macrophages and recruited (and activated) neutrophils. Damage in this lung model can be precisely quantitated by extravascular leakage of I2’I-labeled albumin from the blood, extravasation of 51Cr-labeled rat RBC, and build-up of neutrophils (as measured by lung content of myeloperoxidase (MPO) or retrieval of neutrophils from bronchoalveolar lavage (BAL) fluids). Cytokine content is usually measured in BAL fluids, although whole lung homogenates can also be employed. The IgG immune complex model may provide information relevant to an understanding of human inflammatory diseases triggered by deposition of IgG immune complexes, such as rheumatoid arthritis, systemic lupus erythematosus, vasculitis, membranous glomerulonephritis, idiopathic pulmonary fibrosis, etc.