The long-range goal of this proposal is to define the immunobiology of human tissue macrophages (MP). What must be determined is whether there is diversity among human MP and then to learn if the diversity is the result of: (1) differential maturation of a single cell line; (2) multiple cell lines; or (3) the presence of autonomous populations, and how different functions may be expressed in each instance. Thus, the more immediate objective is to resolve the issue of MP heterogeneity, i.e., can human tissue MP (like lymphocytes) be grouped into distinct phenotypic and functional subpopulations? The spleen provides an ideal tissue for testing our hypothesis that there are functionally distinct MP subpopulations in the human because it is regularly available and because multiple tissue MP phenotypes in different locations appear to be present; furthermore, the data generated from the study of splenic MP will provide the necessary requisites for resolving the issue of the basis for MP diversity.
The specific aims are: (1) to determine if discrete phenotypic MP subpopulations can be identified in situ and in MP-enriched suspensions by morphologic, ultrastructural, histochemical, and antigenic techniques; (2) to isolate MP subpopulations with distinct phenotypes, determine the presence of multiple antigens on these subpopulations, and test the stability of selected markers; and (3) to correlate specific MP subset phenotypes with selected functions, including immunoregulatory and accessory cell functions, hematologic homeostasis, and clearance of specific circulating pathogens. (MB)
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