The proliferation kinetics of murine and human mononuclear phagocytes will be studied. The relationship between factors which are required for and promote proliferation and those which inhibit proliferation will be defined. It is our belief that once we understand how proliferation is regulated we will be able to alter the host's environment during disease states to mobilize effective numbers of mononuclear phagocytes. No natter how much we try to reduce the burden of pathogenic organisms or tumor burden which these normal host defense cells combat, they will be ineffective if there are too few available. We are also studying mononuclear phagocyte proliferation in order to provide clones of these cells in large enough numbers to study their functional heterogeneity. Using the Flow Cytometer and Cell Sorter, we will study differentiation of mononuclear phagocytes as they proliferate. By removing the growth factors we can also study their differentiation in the absence of proliferation. We plan to study the following markers of differentiation: The rate of adherence of progeny derived from nonadherent bone marrow progenitor cells, the development of phagocytosis and the development of membrane markers for Ia, Fc receptors and C3b receptors. We will be able to determine from these studies whether functions or markers expressed by monouclear phagocytes represent differentiated states through which all cells pass or whether some functions are of clonal origin and unique to a discrete subpopulation of cells.
