Effect of human monocyte-released cytostatic factors on target cell DNA synthesis, protein synthesis, and ATP content

Cultured human monocytes activated in vitro with lymphokines and lipopolysaccharide release cytostatic protein factors that may be separated by ion-exchange chromatography into two populations, termed cytostatic factors I and II (CF I and II). The effect of CF I and II on target cell DNA synthesis, protein synthesis, and ATP content and the possible presence of a CF-associated protease activity were investigated. Inhibition of DNA synthesis was detected 4 h after addition of either CF I or CF II, whereas inhibition of protein synthesis was first detected after 10-15 h. Moreover, 20 h after addition of either CF I or CF II the average DNA synthesis per cell was inhibited by 25-35%, as compared with 10-15% inhibition of protein synthesis. No significant alteration in cellular ATP content was observed in cells culture up to 25 h with either CF I or CF II. Thus, neither protein synthesis nor generation of ATP appeared to be primary targets of either CF I or CF II, but the factors may act more directly on DNA synthesis. Protease activity was not associated with either CF I or CF II, and the factors thus differed from a previously reported cytolytic protease released from activated murine macrophages.