Inhibition of Borrelia burgdorferi-bound fibrinolytic enzymes by alpha(2)-antiplasmin, PAI-1 and PAI-2

Lyme disease is caused by Borrelia burgdorferi. Human plasminogen and urokinase-type plasminogen activator bind to the surface of the spirochete where plasmin is generated. We have suggested that bound urokinase and plasminogen are utilized by the organism to disseminate. We tested whether the physiological inhibitors of urokinase, plasminogen activator inhibitor-1 and -2 (PAI-I, PAI-2), could regulate the activity of spirochete-bound urokinase. The k(ass) of PAI-1 and PAI-2 for bound urokinase were 1.3 x 10(6) M(-1)s(-1) and 6.9 x 10(4) M(-1)s(-1) respectively, whereas the k(ass) for free urokinase were 7.2 x 10(6) M(-1)s(-1) and 5.3 x 10(5) M(-1)s(-1), respectively. Plasmin associated with the spirochete was not inhibited by alpha(2)-antiplasmin. These results suggest that PAI-1, PAI-2 and alpha(2)-antiplasmin would not be efficient regulators of fibrinolytic protease activity on the Borrelial surface and would nor pose a barrier to utilization of these enzymes for dissemination in the human host. (C) 1996 Academic Press. Inc.