Colony stimulating activity (CSA) and burst promoting activity (BPA) are glycoprotein molecules which stimulate, respectively, clonal granulopoiesis and erythropoiesis in vitro. CSA and BPA are produced by a variety of cell types including mononuclear phagocytes, T-lymphocytes, fibroblasts, and endothelial cells. Until recently, little was known about the mechanisms which might orchestrate production by such heterogeneous cells. We have described soluble factors produced by mononuclear phagocytes which stimulate CSA and BPA production by T-cells, fibroblasts, and endothelial cells. These factors we have termed monocyte-derived recruiting activity for CSR (MRA?CSA?) and for BPA (MRA?BPA?). Our studies are designed to test the hypothesis that MRA is a biologically relevant regulator of hematopoiesis. We intend: (1) to purify MRA and analyze the granulopoietic specificity of MRA by distinguishing it functionally and chemically from monokines which are known to influence the proliferation of mesenchymal cells and erythroid progenitor cells; (2) to identify mechanisms by which MRA is produced in vitro; (3) to identify mechanisms by which MRA exerts its stimulatory effect on CSA- and BPA-producing target cells; (4) to determine the influence of MRA-induced CSA on patterns of granulocyte/monocyte differentiation of both leukemic and normal hemopoietic progenitor cells in vitro; and (5) to quantitate MRA in urine, serum, and cell supernatants from patients with chronic granulocytic leukemia, polycythemia vera, and patients with congenital or acquired neutropenia. These studies will better define the role of these newly recognized monokines in the regulation of granulopoiesis. (J)
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