The response of the fibrinolytic system to mycobacteria infection

Abstract

The human pathogen Mycobacterium tuberculosis binds to a variety of host cell proteins, including those of the fibrinolytic system. These observations prompted us to study the expression of components of this system in an animal model of progressive pulmonary tuberculosis. Lung homogenates from BALB/c mice infected with M. tuberculosis H37Rv were analyzed to determine the expression and enzymatic activity of plasmin/plasminogen and tissue plasminogen activator, as well as the mRNA levels for plasminogen, tissue and urokinase plasminogen activators. Plasminogen was also detected in infected lungs with immunohistochemistry. The results show that the expression of molecules of the fibrinolytic system increased gradually over the course of the infection, peaking during the chronic phase of the disease. Furthermore, in vitro experiments showed that both plasminogen activators were specifically induced after the stimulation of spleen cells from BCG-immunized mice with M. tuberculosis proteins. Together, these results show that molecules of the fibrinolytic system are up-regulated in the chronic phase of experimental tuberculosis and suggest that the mycobacterium itself could play an important role in the overexpression of molecules of the fibrinolytic system, contributing to chronic inflammation in tuberculosis.