The overall objective of this research is to characterize the process of differentiation of human monocytes-macrophages from the precursor cells in bone marrow and in the peripheral blood to the macrophage stage with particular emphasis on the variation of antigenic expression and on the development of specific functions. The experimental models used will include: (1) established lines of human hematopoietic cells and primary cultures of leukemia cells induced to differentiate in vitro by different chemical or biological inducers; and (2) in vitro growth and differentiation of normal precursor and stem cells from bone marrow and peripheral blood. The general aims are to determine whether an imbalance in the expression of surface markers during induced differentiation of these cells exists. One of the results of the first year of this project was the finding that immune interferon induces both the receptor for the Fc fragment of monomeric IgG and differentiation aIong the monocytic lineage in myeloid cells. The current studies are mostly focused to analyze these effects of immune interferon and to compare them with those of other chemical and naturally occurring inducers. Immune interferon is effective both on immature and differentiated cells of the myelomonocytic lineage. In immature myeloid cells, both normal and leukemic, immune interferon induces differentiation, with acquisition of monocytic markers and functions and loss of proliferative ability. On differentiated cells (granulocytes, monocytes, macrophages), immune interferon acts as an activation factor, inducing increased expression of HLA-DR and Fc receptor, enhanced phagocytosis, antibody-dependent celI-mediated cytotoxicity, lysosomal enzyme release, and increased oxidative metabolism. (MB)