The investigators have established that human pulmonary alveolar macrophages express three distinct receptors for the Fc domain of IgG (Fc gamma receptors). The function of each of these three Fc gamma receptors, Fc gamma RI, Fc gamma RII and Fc gamma RIII, on normal human macrophages is unknown. Furthermore, it is unclear as to why human macrophages express three different Fc gamma receptors. The presence of multiple tissue macrophage Fc gamma receptors suggests that these receptors perform different important functions. The investigators' goal is to determine the function of each of these pulmonary macrophage Fc gamma receptors. The investigators' hypothesis is that each pulmonary macrophage Fc gamma receptor has a functional role which distinguishes it from the other Fc gamma receptors. The investigators also predict that these functions will be important in the host defense of the lung and/or in the interaction with immune complexes in the lung. Pulmonary macrophages are a model for normal tissue macrophages. They are also the most readily available normal tissue macrophage for in vitro study. Pulmonary macrophages also are of importance because of their significant role in lung host defense and in the pathophysiology of pulmonary immunologic and granulomatous disorders. The study of pulmonary macrophages enables one to examine not only normal macrophages, but also the in vivo effect of pulmonary disorders on tissue macrophage Fc gamma receptors. The investigators have chosen to study two pulmonary macrophage Fc gamma receptors, Fc gamma RII and Fc gamma RIII, in two granulomatous disorders of the lung, sarcoidosis and berylliosis, where these Fc gamma receptors are altered and in which these macrophages play a role in the pulmonary pathology. cDNAs encoding for the three human Fc gamma receptors have recently been isolated and cloned. The investigators have obtained cDNA probes for each of these receptors. These probes and monoclonal antibodies will be used to assess pulmonary macrophage Fc gamma receptor transcription, glycosylation and surface expression. Pulmonary macrophage Fc gamma receptor function will be examined by: 1) measuring IgG ligand binding to each Fc gamma receptor and 2) by determining Fc gamma receptor dependent activation as a functional consequence of IgG ligand binding and Fc gamma receptor cross-linking with monoclonal antibodies. Pulmonary macrophage activation will be assessed by the ability of specific Fc gamma receptors to initiate superoxide production and lysosomal enzyme release. There is evidence from both the applicants' group and other laboratories that Fc gamma receptors on several cells are differentially regulated by endogenous and pharmacologic signals. It is unknown whether such regulation occurs at the tissue macrophage level. The investigators will study the differential response of pulmonary macrophage Fc gamma receptors to regulatory signals known to affect some Fc gamma receptor systems. Pulmonary macrophages are a source of normal and abnormal tissue macrophages accessible for study; in humans they are the only available source. The investigators will take advantage of this to examine in-depth both the expression and function of each distinct class of pulmonary macrophage Fc gamma receptor.
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