The uPA/uPAR System and suPAR in HIV Infection
Pp. 81-101 (21)
Sisse R. Ostrowski, Eva Haastrup, Anne Langkilde, Henrik Ullum and Jesper Eugen-Olsen
The urokinase Plasminogen Activator Receptor (uPAR) is linked to the surface of immune cells
and involved in multiple immune functions including cell adhesion, chemotaxis, migration, angiogenesis,
fibrinolysis, proliferation, differentiation and signal transduction. uPAR binds and activates urokinase
resulting in extracellular matrix degradation and remodeling. Also, uPAR can bind the extracellular matrix
protein vitronectin promoting cell adhesion and migration.
uPAR can be cleaved from the cell surface resulting in soluble uPAR (suPAR). suPAR levels are
increased by various infectious diseases associated with systemic inflammation such as HIV infection.
Several studies have shown that those with the highest suPAR levels have increased disease progression
and high risk of mortality.
Furthermore, uPA was demonstrated to exert antiretroviral activity by inhibiting late steps in HIV
replication cycle in various cell lines, through mechanisms dependent on cell adhesion. Future research
will determine whether the emerging role of the uPA/uPAR/suPAR-system in HIV infection can be
implemented in HIV drug development and in the use of suPAR measurements for initiating antiretroviral
therapy and for monitoring treatment efficacy.
Clinical Research Centre 136, Copenhagen University Hospital, Hvidovre Hospital, Denmark.