Initiation and sustenance of inflammation in the human lung are important for successful defense against antigenic and environmental challenges. Appropriate control and resolution of inflammation are important to prevent induction of permanent reparative fibrosis. The alveolar macrophage is likely to be an important cell for defense of the lung and for maintenance of pulmonary immune homeostasis because of its position at the environment-alveolar epithelial interface and by virtue of its role in the initiation and regulation of lymphocyte immune responses (""""""""accessory cell function""""""""). Significant differences in the accessory cell function of alveolar macrophages and blood-derived monocyte-macrophages have been demonstrated for both mitogen-and antigen-stimulated lymphocyte responses. Such specific differences in immune function may be important, in clarifying the role of alveolar macrophage in defense of the lung. In this research proposal, factors contributing to the differences of the accessory cell function of autologous human alveolar and peripheral blood-derived macrophages are investigated by examining; 1) their respective accessory cell function for the helper/inducer and cytotoxic/suppressor T-lymphocyte subsets, their respective production of factors that either enhance (e.g. interleukins) or suppress (e.g. prostaglandins) lymphocyte proliferation, 2) differential effects of in vitro influenza virus infection on their accessory cell function, 3) aspects of their respective antigen-processing/presentation capabilities and 4) the role of differentiation/maturation in contributing to their functional differences. Information derived from this research should contribute to understanding of control of inflammation in the normal lung and thereby strengthen the foundation for investigation of pathology of flammatory pulmonary disease.
