INTERFERON-GAMMA-INDUCED EXPRESSION OF TISSUE FACTOR ACTIVITY DURING HUMAN MONOCYTE TO MACROPHAGE MATURATION

The expression of tissue factor (TF) during differentiation of human monocytes (MO) to macrophages (MAC) in vitro is investigated in this study. In MO, TF activity can be induced by the addition of lipopolysaccharides (LPS) as detected by Northern blot analysis and measured functionally as procoagulant activity (PCA), while IFNgamma alone has only marginal stimulatory activity. During in vitro differentiation of MO into MAC, however, there is a steady increase in IFNgamma-induced PCA with a maximum on day 7. While MO during the first 2 days in culture are more responsive to LPS, IFNgamma becomes the prominent stimulus for mature MAC. The response to IFNgamma is rapid with a peak within 6-8 h and a subsequent downregulation to baseline activity within 24 h. Our results demonstrate that IFNgamma can effectively induce TF in human MAC and that its expression is developmentally regulated during MO to MAC maturation in vitro.