Alveolar macrophages, cells which have long been regarded only as resident scavengers, are beginning to emerge as pluropotential cells capable of diverse functions. This research project is designed to test the hypotheses that alveolar macrophages can be divided into subpopulations on the basis of size and density, and that individual subpopulations perform specific functions. Alveolar macrophages from rat and human (with and without interstitial pulmonary fibrosis) will be obtained by bronchoalveolar lavage, and cells will be separated into subpopulations by continuous gradient centrifugation and automated flow cytometry. Individual subpopulations will be characterized by size, morphology using light and electron microscopy, surface antigen markers, histochemistry, chemotatic activity, and phagocytic function. Characteristics of alveolar macrophage subpopulations from patients with an without interstitial fibrosis will be compared to determine if shifts in individual subpopulations occur or specific characteristics are altered. This may provide clues as to the role of alveolar macrophages in interstitial pulmonary fibrosis. Ultimately, the goal of this research project is to determine if subpopulations of macrophages secrete factors which stimulate pulmonary fibroblasts to replicate and secrete collagen. Understanding this process may eventually lead to therapeutic modalities which can arrest collagen production and halt the progression of interstitial pulmonary fibrosis.
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