Myeloid cells (monocytes (Mo), macrophages (M0) and polymorphonuclear neutrophils (PMN) play profound roles in both the inductive and effector phases of an immune response. We have recently begun to develop an integrated understanding of how the modulation by immune cytokines of particular surface molecules on myeloid cells results in a physiologically relevant change in cell function. For example, during streptococcal infections, IFN-gamma increases the oxidative killing mechanisms of myeloid cells, and also increases the surface expression of the recognition molecules (IgG Fc receptors or FcgammaR) which recognize antibody-opsonized bacteria. Although myeloid cells are present and functional in the female reproductive tract, very little is known about the influence that the menstrual cycle, menopause, hormones such as oral contraceptives, estrogens etc., and other cells of the reproductive tract have on myeloid cell phenotype and function. The hypothesis to be examined in this proposal is that stage of the menstrual cycle, cytokines, sex hormones and local tissue factors influence the phenotype and function of myeloid cells within the reproductive tract. Our approach will be to determine whether myeloid cells isolated from the reproductive tract and from peripheral blood of the same person are similar or different with respect to 1) surface phenotype as determined by monoclonal antibody binding and flow cytometry, 2) cytolytic and phagocytic capacity determine in cell culture assays, 3) ability to present antigen in T-cell stimulation assays and 4) using co-cultures of immune cells and uterine epithelial cells, the influence of hormone- induced epithelial cell products (such as the glucocorticoid-induced anti-inflammatory protein lipocortin 1) on immune cell phenotype and function. Each of these studies would include an evaluation of the response to immune cytokines and steroid hormones in terms of phenotype and function. The information obtained with both established the basic characteristics of myeloid cells in the female reproductive mucosa, and will define the direct and indirect influence of sex hormones and mucosally derived factors on these parameters.
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