Infection of the transplanted lung is the greatest single threat to long term survival of heart-lung recipients. Immunosuppression certainly contributes to the increased risk of infection in the transplanted lung, but the observation that pulmonary infection in heart recipients, who are immunosuppressed, to the same degree as lung recipients is much less frequent suggests that there are factors peculiar to the transplanted lung which predispose it to infection. the alveolar macrophage plays a crucial role in defending the normal lung against inhaled microorganisms. To be effective this cell must be able to migrate toward microorganisms, ingest and kill them, recruit additional cells to an infected alveolus by releasing chemotactic factors for circulating phagocytes and to initiate an immune response. Results of preliminary studies suggest there is impairment in several functions of macrophages from lung recipients which may reach profound proportions. The cause of this impariment and the clinical implications for the individual recipient are not known. The purpose of this study is to assess to vitro migratory activity, phagocytosis and killing of candida tropicalis, production of chemotactaxins for neutrophils and monocytes and accessory cell activity for antigen induced lymphocyte proliferation of macrophages from lung recipients, heart recipients and normals to determine the severity of impairment of these functions in transplant recipients, factors within the lung recipient that are associated with impairment and if there are products unique to the airspace of the transplanted lung which adversely affect the function of the airspace macrophage. Macrophages and alveolar fluid will be obtained sequentially from heart-lung recipients by bronchoalveolar lavage and the level of macrophage function correlated with immunosuppression, origin of the macophage, presence of CMV in the macrophage, the presence of bacterial and pneumocystis infection in the lung and the clinical course of the lung recipients. Studies on cells from heart recipients will provide information about the effect of immunosuppression on the function of macrophages from a normal lung. Lavage fluid from lung recipients and heart recipients will be added to cultures of normal macrophages to determine if there are factors in the airspaces of the allograft that inhibit the function of normal macrophages in vitro. Results should indicate if impaired clearance functions of macrophages in vitro are associated with an increased risk of infection in the transplanted lung and may provide insight into mechanisms of this impariment.
