Abstract
The lung, like most other organs, is susceptible to injury by circulating immune complexes, and also by humoral autoantibody and immune lymphocytes which specifically recognize selected lung antigens. In addition, by virtue of its direct communication with the external environment, the lung can also be injured by inhaled environmental agents which trigger inflammatory reactions mediated by immune effector systems. Although major emphasis to date has been placed on the ability of inhaled antigens to first sensitize, then provoke, immunologically specific reactions in the lung, there is increasing evidence to show that these same immune effector systems are also triggered in an immunologically nonspecific fashion by a certain environmental agents (termed "mitogens") which activate leukocytes in a polyclonal fashion. Such agents include certain viruses and other microorganisms, bacterial endotoxin, a wide variety of plant lectins, and certain chemicals, such as the phorbol esters. Although such agents act in an immunologically nonspecific fashion, they are nonetheless quite specific from a chemical viewpoint, and in many cases act by binding to specific receptors on the cell surface. By activating macrophages directly, and by activating much larger percentages of a given lymphocyte population than do specific antigens, they induce correspondingly amplified inflammatory reactions in vivo. Recent studies with animal models indicate that inhaled mitogens are strikingly effective in inducing pulmonary inflammation, whereas inhaled antigens (lacking mitogenic activity) produce little if any parenchymal injury in immunized recipients, unless administered in conjunction with a mitogen. Ongoing studies using such models promise to provide valuable new insight into the biologic properties which govern the pathogenicity of inhaled environmental agents, the mediators they release, and the biochemical basis for variations in individual susceptibility to injury by such agents.