Abstract
We compared urokinase-type plasminogen activator (u-PA) in fluid phase and u-PA bound with its receptor on human blood monocytes with respect to proteolytic activity and susceptibility to inactivation by the plasminogen activator inhibitors PAI-1 and PAI-2. Receptor-bound u-PA is catalytically twice as efficient as fluid-phase u-PA. Fluid-phase u- PA is susceptible to rapid inhibition by PAI-1 and PAI-2 at an estimated PAI:u-PA molar ratio of 2:1. In contrast, u-PA bound to endogenously occupied receptors is inhibited by PAI-2 only at PAI:u-PA molar ratios of 20:1, but is not inhibited by PAI-1, u-PA/PAI-1 and u- PA/PAI-2 complexes bind to the receptor with a tenfold lower affinity than u-PA itself. Thus, competition of u-PA/PAI complexes with fluid- phase u-PA for binding to the receptor is unlikely to affect the overall plasminogen activator activity of the monocyte. These findings demonstrate that the activity of receptor-bound u-PA can be modulated by PAI-2, but not by PAI-1, to adjust the cell's proteolytic activity to different local situations.
