Lymphokine stimulation of human macrophage C2 production is partially due to interferon-gamma.
Monocyte complement stimulator (MCS), a product of T lymphocytes, is defined by its ability to stimulate the synthesis and secretion of the second complement component (C2) by monocytes. Most macrophage-activating factor (MAF) activity present in lymphokine-rich culture supernatants has recently been found to be due to interferon-gamma (IFN-gamma). We therefore hypothesized that IFN-gamma may have MCS activity as well. We tested recombinant, E. coli-derived, human IFN-gamma (rIFN-gamma) for its effects on C2 production by adherent peripheral blood monocytes and U937 cells, a human monocytic cell line. Recombinant IFN-gamma in concentrations ranging from 0.1 to 300 U/ml (0.003 to 8.8 ng/ml) stimulates C2 production by both cell populations. Exposure of responding cells for at least 24 hr is required for maximal stimulation. To determine the contribution of IFN-gamma toward total MCS activity in crude lymphokine-rich supernatants, we employed a solid-phase immunoabsorption technique with the use of a monoclonal anti-IFN-gamma antibody. This technique removed all IFN-gamma detectable by a sensitive ELISA, but MCS activity was decreased by only 40 to 50%. Additionally, MCS activity of these supernatants did not correlate with IFN-gamma content as determined by ELISA. By using another method to eliminate IFN-gamma activity, acid dialysis destroyed all rIFN-gamma activity, as measured by stimulation of U937 C2 synthesis, but eliminated only 30 to 67% of MCS activity from crude lymphokine preparations. Thus IFN-gamma stimulates C2 production by monocytes and U937 cells and apparently accounts for some, but not all, MCS activity present in lymphokine-rich supernatants. Other lymphokines are present in such supernatants that also possess this activity.
D002460:Cell Line; D003175:Complement C2 / Q000096:biosynthesis*; D003956:Dialysis; D006801:Humans; D007163:Immunosorbent Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008222:Lymphokines / Q000494:pharmacology*; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D003175:Complement C2; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D011994:Recombinant Proteins; D007371:Interferon-gamma