The long-range goal of this research is to define the immunobiology of the macrophage (Mphi). The immediate objective is to understand the basis of Mphi functional heterogeneity. We recently found that mouse bone marrow cells, immortalized by DNA transfection, produce such high levels of a Mphi colony-stimulating factor that it is now possible to obtain cloned Mphi populations with sufficient numbers of cells for phenotypic and functional analyses. With the mouse as an experimental model, I will determine (i) if distinct lineages of antigen-presenting Mphi exist, (ii) whether monoclonal antibodies detect phenotypically distinct and stable subsets of Mphi, (iii) if selected homeostatic and host-defense functions of the spleen reside with phenotypically distinct and independent lineages of Mphi and, (iv) whether or not distinct factors regulate the proliferation and differentiation of different Mphi populations. In addition to their roles in host-defense and homeostasis, Mphi are now recognized to participate in the development of certain human diseases such as arteriosclerosis and, possibly, multiple sclerosis. If such roles are limited to distinct subpopulations of Mphi, then the information gained from this study might make it possible to manipulate them to therapeutic advantage.
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