Heterogeneity of function is increasingly recognized as a characteristic feature of unfractionated preparations of alveolar macrophages. Work performed to date on this project has established differences in immunologic functions among aveolar macrophages fractionated according to cell density. This proposal is designed to investigate potential determinants of these functional differences among lavaged rat aveolar macrophages. The long-term objective of this project is to examine modulation of alveolar macrophage function as a possible mechanism for regulating pulmonary immune reactivity. Our hypothetical model proposes that heterogeneity of alveolar macrophage function arises from the interplay of three factors: the influx of monocytes from the blood, the activation of macrophages resident in the lung, and the efflux of mature macorphages to conducting airways.
The Specific Aims are: 1) To determine the role of monocyte recruitment from peripheral blood in the generation of functional assays to determine how monocyte influx into the lungs contributes to heterogeneity; 2) To determine the effects of pulmonary inflammation on functional differences among lavaged alveolar macrophages. Granulomatous pulmonary inflamation will be induced by the administration of BCG, and density fractionated macrophages will be assayed functionally to determine whether pulmonary inflammation alters functional heterogeneity of the cell preparations; 3) to examine the role of alveolar macrophage ellux to the airways as a determinant of functional heterogeneity. Alveolar macrophages, harvested from the trachea and large airways will be assayed for cell size, Ia expression, and ectoenzyme activity in order to determine whether cellular migration to the airways from the alveolar spaces is a random or a selective process. Information gained from these studies should help define factors influencing heterogeneity of immunologic function of alveolar macrophages and perhaps suggest their role in host defenses or in the induction of lung diseases.
