The lung is a primary target for constant exposure to foreign configurations which include infectious organisms, allergens and environmental pollutants. The potential for pulmonary disease would remain extremely high as a result of this persistent insult were it not for the operation of normal lung defense mechanisms which include the combined action of the mucociliary, phagocytic and specific immune systems. It has been suggested repeatedly that the alveolar macrophage (AM) plays an important role in lung defense, however, the precise function of this cell in the specific immune response is still unclear. While some studies propose that the function of the AM is to remove antigen from the potential immunogenic pool thereby limiting immune responses which occur in the lung, there are numerous inferences, with little data to support them, that AM are functionally similar to macrophages obtained from more frequently studied anatomical locations (peritoneum and spleen) in that they provide accessory function by interacting with lymphocytes in the afferent and efferent arms of the immune response. Our previous work has indicated that AM are capable of regulating immune responses as demonstrated by their inability to present antigen effectively for the initiation of an immune response by suppressing antibody production and by enhancing cell-mediated immune functions. These observations suggest that the AM may play a central role in protecting the host from pathological lung injury. It is the intent of this proposal to further define the regulatory functions of AM. Experiments have been designed to study the interaction of AM with lung-associated lymphoid cells asking questions germain to the understanding of AM functions in humoral and cell-mediated immune responses. We will provide further insight into determining the mechanisms involved in the regulation of immune responses by AM. We will amplify our observations from animals models to study AM function in normal humans and patients with pulmonary disease using established in vitro assays of immune function to gain further understanding of the complex function of AM in protection against human lung disease.
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