BORRELIA BURGDORFI INDUCES SECRETION OF PRO-UROKINASE-TYPE PLASMINOGEN-ACTIVATOR BY HUMAN MONOCYTES

Borrelia burgdorferi is transmitted by infected ticks and causes Lyme disease, To infect distant organ sites, B. burgdorferi spirochetes mus t disseminate from the site of the tick bite. During dissemination fro m the dermal tissue, they breach tissue barriers, probably by proteoly sis, The previous findings that spirochetes bind serum-derived plasmin ogen and that plasmin favors spirochetal invasiveness and infectivity suggested a role for plasmin in the pathogenicity of B. burgorferi. Bi nding of plasminogen to spirochetes and activation into plasmin is fav ored in a microenvironment that is rich in plasminogen and plasminogen activators. Plasminogen is abundant in plasma and interstitial fluids , and it is increased in inflammatory exudates. Since B. burgdorferi d oes not express endogenous plasminogen activators, the conversion of s pirochete-bound plasminogen depends on host-derived plasminogen activa tors. In this report, we show that both intact B. burgdorferi organism s and its recombinant outer surface lipoprotein A induce human monocyt es to express and secrete urokinase-type plasminogen activator in its zymogen form (pro-uPA), Moreover, we demonstrate that the presence of B. burgdorferi accelerates the interaction between (pro-)uPA and plasm in(ogen), leading to spirochete-bound plasmin, In a pro-uPA-serum mixt ure, spirochete-bound plasmin activity is generated, Taken together, t he data suggest that B. burgdorferi may induce pro-uPA in a monocyte-c ontaining inflammatory site and that the spirochetal surface provides an appropriate milieu for subsequent interactions between (pro-)uPA an d plasmin(ogen), which result in spirochete-bound plasmin even in the presence of inhibitors for plasminogen activators and plasmin.