Reciprocal upregulation of urokinase plasminogen activator and its inhibitor, PAI-2, by Borrelia burgdorferi affects bacterial penetration and host-inflammatory response.
The mammalian plasminogen activation system (PAS) is a complex system involved in multiple physiological and pathological processes. Borrelia burgdorferi interacts with certain components of the PAS. Here we further investigate this interaction to determine its effect on bacterial dissemination and host cell migration in vitro. We show that stimulation of monocytic cells with B. burgdorferi induces the transient production and secretion of urokinase plasminogen activator (uPA), shortly followed by its physiological inhibitor, plasminogen activator inhibitor-2 (PAI-2). Mono Mac 6 (MM6) cells as well as peripheral blood monocytes enhanced transmigration of B. burgdorferi across a barrier coated with fibronectin mediated by uPA. Moreover, the induction of PAI-2 or the addition of recombinant PAI-2 did not have a significant effect on the uPA-potentiated transmigration of B. burgdorferi. In contrast, the induction of PAI-2 by B. burgdorferi resulted in significantly diminished invasion by monocytic cells across a reconstituted basement membrane (matrigel), which could be partially restored by treatment with purified uPA. These results show that the PAS plays a twofold role in the pathogenesis of B. burgdorferi infection, both by enhancing bacterial dissemination and by diminishing host-cell inflammatory migration.
Haile
Woldeab B
WB
Center for Infectious Diseases, Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794-5120, USA.
Coleman
James L
JL
Benach
Jorge L
JL
D025065:Borrelia burgdorferi / Q000472:pathogenicity* / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D007249:Inflammation / Q000209:etiology; D009000:Monocytes / Q000382:microbiology; D017396:Plasminogen Activator Inhibitor 2 / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000502:physiology*; D014774:Virulence / Q000502:physiology
D017396:Plasminogen Activator Inhibitor 2; D014568:Urokinase-Type Plasminogen Activator