The goal of our research is to enhance understanding of the pulmonary alveolar macrophage (PAM) in health and disease. These cells are the only members of the mononuclear phagocytic system in direct contact with the external environment. It is well known that these cells ingest inert particles and kill pathogens on the lung surface. More recently it has become evident that secretory products of PAMs may regulate inflammatory responses in the lung. The central hypothesis of this project is that PAMs have unique specialized features which facilitate interaction with the external environment and their function on the lung surface. Two such features which appear to be related have been identified in our laboratory: 1) PAMs ingest unopsonized inert particles more avidly than any other phagocytic cell type, and 2) there is a specific antigen on the surface of PAMs of hamsters (HAM1) which develops after these cells appear on the alveolar surface. Monoclonal antibodies to HAM1 have been produced and these antibodies block ingestion, but not binding, of proposed research seeks to determine specific HAM1-like antigens on these cells. Two new hypotheses which are extensions of our central hypothesis will also be tested in the proposed studies. The first is that HAM1-like antigens and receptors for opsonin independent phagocytosis develop under similar influences, but they are distinctive membrane structures. The functional, biochemical, and anatomic relationships between antigens and these receptors will be defined for human and hamster PAMs. To better understand the specialization of HAM-1 like antigens, the gene(s) responsible for their expression will be identified and cloned. The second hypothesis is that PAMs not only use distinctive pathways for phagocytosis of inhaled particles, but respond to the ingested material in a manner predictable by the pathway. Using opsonized and unopsonized latex beads as well as zymosan and other digestible materials, the determinants and magnitude of macrophage responses to ingested materials will be studied. The lung has a second macrophage population, the interstitial macrophages (IMs), which are nearly equal in number to PAMs. The response of IMs to particle ingestion will be contrasted to PAMs to characterize their role in cellular responses which may result in pulmonary disease.
