INTERFERON AS A MACROPHAGE ACTIVATING FACTOR .1. ENHANCEMENT OF CYTO-TOXICITY BY FRESH AND MATURED HUMAN-MONOCYTES IN THE ABSENCE OF OTHER SOLUBLE SIGNALS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 51  (3) , 501-510
Abstract
The cytolytic activity of human peripheral blood monocytes in vitro against K-562 human leukemic target cells was stimulated by human fibroblast (.beta.-) and leukocyte (.alpha.-) interferon (IFN). Stimulation was by up to several times the corresponding control activity, and was observed with freshly isolated monocytes, and with monocytes cultured for various periods up to 10 days. The cytolytic activity of untreated monocytes was detectable at very low effector:target ratios (< 5:1), and fell between days 1 and 4 in culture, normally rising again towards the initial activity at day 8; this pattern was also observed when IFN was present continuously, although the activities were then always higher than in the corresponding control cells. Cytolysis showed a lag of about 6 h, in contrast to that by natural killer (NK) cells, and was routinely measured over 24 h. The course of stimulation by IFN and its dose-response were studied. Stimulation required the presence of IFN for at least 24 h, and was maximal between 1000 and 10,000 U of IFN/ml. When IFN-containing media were removed and replaced with control media, the monocyte activity remained stimulated for at least 4 days. Stimulation by .beta.-IFN was blocked by a specific antibody to .beta.-IFN, under conditions in which assayable IFN activity was also neutralized. Several control experiments indicated that the action of IFN was on the monocytes and not on the target cells. The morphological maturation of monocytes was retarded by IFN, even in cultures containing up to 50% serum. The effectiveness of fibroblast IFN indicated that stimulation could not be attributed to the lymphokines which might contaminate .alpha.-IFN. The action of IFN did not require simultaneous or antecedent in vitro stimulation by endotoxin. This was indicated both by serum free experiments, and also by others in which polymixin B was used to complex with and render unavailable any endotoxin present. Endotoxin showed an independent stimulatatory effect, which could be prevented by polymixin.