Induction of Fc receptors on murine macrophages and leukemic cells by interleukin-1 beta.

Recombinant human interleukin-1 beta (rhIL-1 beta) is shown to be a strong inducer of Fc receptors (FcR) on murine macrophages and not on granulocytes. Data is provided indicating that rhIL-1 beta does induce specific but not nonspecific phagocytosis. Macrophages are shown to autoinduce their FcR expression as a function of time in culture. This induction is increased by the use of exogenous rhIL-1 beta and inhibited by anti-rhIL-1 beta antibody, pointing to an autocrine regulation of FcR expression on macrophages. On the other hand the myelomonocytic cell line WEH13BD- and the macrophage like cell line WR19M.1 are also shown to be inducible for the expression of FcR by this molecule. Data is also provided showing that recombinant murine Interferon gamma (rmIFN gamma) induces FcR on both macrophages and granulocytes. Whereas polyclonal antibodies inhibit FcR induction by IL-1 on macrophages, it does not inhibit FcR induction by IFN gamma on these cells. This points to a different mechanism of induction of FcR by IFN and IL-1. Finally, the possible application of rhIL-1 beta in vivo to help the organism fight infections is discussed.

Evidence that G-CSF is a fibroblast growth factor that induces granulocytes to increase phagocytosis and to present a mature morphology, and that macrophages secrete 45-kd molecules with these activities as well as with G-CSF-like activity.

Evidence is provided that conditioned medium from a macrophage-like cell line contains molecules of approximately 45 kd molecular weight with granulocyte colony-stimulating factor (G-CSF)-like activity as well as with the property of inducing granulocytes to phagocytose latex particles and to mature morphologically. This type of differentiation was found to be induced on either bone marrow or induced granulocytes, but not on resident or induced macrophages. On the other hand, resident but not induced macrophages are shown to induce these types of activities when challenged by bacterial lipopolysaccharides. Evidence that macrophages produce a factor that is mitogenic for fibroblasts is also provided. This activity was measured by the induction of increased proliferation by either low-density or saturated cultures of fibroblasts. Human recombinant G-CSF was employed and found also to possess these dual capabilities of inducing both the proliferation and differentiation of granulocytes as well as the proliferation of fibroblasts. Finally, a mechanism for the regulation of myeloid cell production and differentiation is described in which G-CSF produced by macrophages not only induces granulocytes to differentiate but induces fibroblasts to proliferate and secrete macrophage colony-stimulating factor (M-CSF), which in turn makes myeloid monocyte precursors proliferate and secrete more G-CSF.