UNLABELLED Streptococcus canis is a zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. Surface-exposed M proteins and metabolic enzymes have been characterized as major virulence determinants in various streptococcal species. Recently, we have identified SCM, the M-like protein of S. canis, as the major receptor for miniplasminogen localized on the ba...

Tissue scarring, characterized by cell activation, excessive deposition of ECM, and extravascular fi brin deposition, is considered a limiting factor for tissue repair. Fibrin, the major substrate of the serine protease plasmin, is a provisional matrix deposited after vascular injury (Bugge et al., 1996). The two plasminogen activators (PAs), namely tissue plasminogen activator (tPA) and urokin...

Borrelia burgdorferi is the causative agent of Lyme disease, the most commonly reported arthropod-borne disease in the United States. B. burgdorferi is a highly invasive bacterium, yet lacks extracellular protease activity. In order to aid in its dissemination, B. burgdorferi binds plasminogen, a component of the hosts' fibrinolytic system. Plasminogen bound to the surface of B. burgdorferi can...

The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomo...

The mammalian protease plasminogen can be activated by bacterial activators, the three-domain (alpha, beta, gamma) streptokinases and the one-domain (alpha) staphylokinases. These activators act as plasmin(ogen) cofactors, and the resulting complexes initiate proteolytic activity of host plasminogen which facilitates bacterial colonization of the host organism. We have investigated the kinetic ...

With the availability of a method of purifying plasminogen from human Fraction IIL8 the therapeutic use of this enzyme in thrombotic conditions became a distinct possibility. Before attempting the clinical use of purified plasminogen, however, it appeared advisable to investigate the reporte that the enzyme responsible for the fibrinolytic activity can be separated from the agent producing prot...

The capacity of cells to interact with the plasminogen activator, urokinase, and the zymogen, plasminogen, was assessed using the promyeloid leukemic U937 cell line and the diploid fetal lung GM1380 fibroblast cell line. Urokinase bound to both cell lines in a time-dependent, specific, and saturable manner (Kd = 0.8-2.0 nM). An active catalytic site was not required for urokinase binding to the...

The mechanism of plasminogen activation by recombinant staphylokinase was studied both in the absence and in the presence of fibrin, in purified systems, and in human plasma. Staphylokinase, like streptokinase, forms a stoichiometric complex with plasminogen that activates plasminogen following Michaelis-Menten kinetics with Km = 7.0 microM and k2 = 1.5 s-1. In purified systems, alpha 2-antipla...

BACKGROUND The expression of the tissue plasminogen activator gene can be affected by histone deacetylation inhibition and thus appears to be under epigenetic control. OBJECTIVES The study aimed to test if in vivo pharmacological intervention by valproic acid treatment would lead to increase in tissue plasminogen activator release capacity. METHODS In an anaesthetized pig model, a controlle...

OBJECTIVE Previous studies have shown that in patients with ANCA-associated vasculitis (AAV), anti-plasminogen antibodies were associated with reduced renal function and the presence of fibrinoid necrosis and cellular crescents in renal histology. The purpose of the current study was to investigate whether anti-plasminogen antibodies are associated with the systemic disease activity of AAV. M...