The purpose of these studies is to investigate the physiologic role in respiratory tract of colony stimulating factors (CSFs) which are active in cells of macrophage lineage. Macrophages are known to be a key aspect of lung defenses against infectious and neoplastic agents, however macrophages may also contribute to lung injury during certain chronic inflammatory states in which the number and functional activity of lung macrophages are increased. The factors which regulate macrophage number within the lung therefore play a pivotal role in both health and disease. In these studies, the physiologic role of CSFs in the maintenance and modulation of lung macrophage populations during steady state and emergency conditions will be investigated. All studies will be performed in a murine system to take advantage of the availability of recombinant macrophage active CSFs which have bioactivity in this species, as well s the availability of DNA probes complementary to CSF genes in the mouse. A comprehensive examination of parameters reflecting CSF bioactivity or production within the lung will be made. These studies include the isolation and characterization of lung macrophage populations retrieved from broncholavage and enzymatic disaggregation of lung parenchyma; measurement of CSF bioactivity in concentrated lavage samples; assessment of macrophage proliferation; identification of CSF producing cells in the lung via in situ hybridization with CSF cDNA probes. Studies are also planned in which recombinant CSFs are administered systemically or by aerosol to determine the effect on macrophage population size and function, potential therapeutic efficacy in experimental models of infection, and the toxicity of this approach.
