Macrophage Cell Lines Behave as Activated Macrophages in the Production and Regulation of Plasminogen Activator

Abstract

Seven macrophagelike cell lines, WEHI-3, J774, RAW264, FC-1, P388D-1, PU5-R, and PU5-1.8, commonly used as in vitro models of macrophage function were studied for their fibrinolytic activity in the presence and absence of purified plasminogen. All cell lines, as well as the freshly harvested peritoneal macrophages, produced plasminogen activator, as indicated by the levels of fibrinolytic activity in the presence of plasminogen. However, fibrinolytic proteolysis was most efficiently measured by direct attachment to ¹²⁵I—fibrin plates, a method which measures both secreted and cell-membrane-associated plasminogen activator. Other non-plasminogen-dependent fibrinolytic activities were also produced by all cells studied and secreted by WEHI-3, FC-1, RAW-264, and thioglycollate-elicited macrophages. Activation of the thioglycollate-elicited macrophages with macrophage activation factor (MAF) induced threefold higher levels of plasminogen activator production but MAF treatment had no effect on the level of activity produced by macrophagelike cell lines. Indeed, the macrophagelike cell lines produced plasminogen activator at levels seen with MAF-activated thioglycollate-elicited macrophages. We conclude that these cell lines constitutively produce activators of plasminogen and, in their failure to respond to MAF, behave as activated macrophages.