ENDOTOXIN-INDUCED INTERFERON SYNTHESIS IN MACROPHAGE CULTURES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 33  (5) , 369-380
Abstract
Pure cultures of murine bone marrow-derived macrophages produce interferon (IFN) after exposure to endotoxin. The levels of endotoxin-induced IFN were enhanced 5- to 20-fold by pretreating (priming) macrophages with murine interferons produced by either Newcastle disease virus induced mouse L cells, which consisted of a mixture of IFN.alpha. and IFN.beta., or IFN.gamma. produced by spleen cells stimulated with phytohemagglutinin. Studies conducted on the kinetics of IFN release from endotoxin-induced macrophages demonstrated that peak synthesis occurred within 2-4 h and was completed 6 h after the start of treatment. The addition of actinomycin D to macrophages, up to 1 h after exposure to endotoxin, completely inhibited release of interferon, thus indicating that gene transcription was required for interferon synthesis. The inclusion of cycloheximide in the medium of endotoxin or Poly(I .cntdot. C)-induced macrophages, although inhibiting 90% of protein synthesis, resulted in a superinducing effect, in that induced macrophages treated with cycloheximide produced higher levels of IFN than macrophages not treated with the inhibitor of protein synthesis. Antigenic characterization of macrophage IFN revealed that endotoxin-induced IFN was neutralized to a higher degree than virus-induced IFN derived from either macrophages or L cells.