GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, BUT NOT MACROPHAGE-COLONY-STIMULATING FACTOR, SUPPRESSES BASAL AND LIPOPOLYSACCHARIDE-STIMULATED COMPLEMENT FACTOR PRODUCTION IN HUMAN MONOCYTES

Monocyte/macrophage contribution of C biosynthesis is important, parti cularly during inflammation. Since granulocyte-macrophage CSF (GM-CSF) and macrophage-CSF (M-CSF) exert a variety of stimulatory effects on monocyte/macrophage functions in vitro, we studied their impact on the biosynthesis of the C components C3 and factor B by human monocytes i n culture. GM-CSF at doses of 10 ng/ml and higher inhibited the basal C3 synthesis. This effect was most pronounced when the cytokine was ad ded to freshly isolated monocytes. No effect was found on the basal pr oduction of factor B. Furthermore, GM-CSF abrogated the LPS-stimulated production of both C3 and factor B. These suppressive effects were ne utralized by a polyclonal anti-GM-CSF antibody. Moreover, when anti-GM -CSF was added to unstimulated or LPS-stimulated cells, their C3 produ ction increased. This indicates that both spontaneous and LPS-triggere d release of monocyte-produced GM-CSF has an autocrine function in reg ulating monocyte C3 biosynthesis. GM-CSF also down-modulated the expre ssion of CD14 at an early stage of cell culture. This might be the mec hanism through which the LPS-effects are suppressed because CD14 has b een shown to be a LPS receptor. Contrary to this, M-CSF at doses of 10 0 U/ml and higher stimulated the synthesis of C3, whereas the basal pr oduction of factor B and the LPS-stimulated production of C3 and facto r B were unaffected. Granulocyte-CSF (G-CSF) did not influence monocyt e C biosynthesis, and neither anti-M-CSF nor anti-G-CSF influenced the LPS-induced C3 production. The effects of GM-CSF and M-CSF on C biosy nthesis may be important in regulating the availability of C component s during an inflammatory response, and these observations may also hav e implications for the clinical use of CSF.