What is suPAR
suPAR (soluble urokinase plasminogen activator receptor) is a protein in the blood.
The plasma level of suPAR reflects immune activation and is increased in several infectious diseases, such as HIV-1-infection, malaria, tuberculosis, Streptococcus pneumonia bacteraemia, sepsis, pneumococcal pneumonia and bacterial and viral CNS infection [1-11]. Furthermore, high suPAR levels are associated with increased inflammation, disease progression and risk of mortality. Measuring suPAR levels can thus serve as a marker to determine chances for survival upon hospital admission as well as for monitoring for prevention of disease progression and earlier intervention time point.
The suPAR protein
suPAR is the soluble form of the urokinase-type plasminogen activator receptor (uPAR), a three domain receptor  mainly expressed on immune cells, including neutrophils, activated T-cells, and macrophages.
Figure 1. Schematic representation of urokinase receptor The GPI-anchor links uPAR to the cell membrane making it available for uPA to bind to the receptor (1 A). When the receptor is cleaved between the GPI-anchor and D3, it becomes soluble (suPAR) (1 B). suPAR is a stable protein that can be measured in various body fluids. uPA: urokinase-type plasminogen activator, uPAR: uPA receptor, suPAR: soluble uPAR, 1: Domain 1, D2: Domain 2, D3: Domain 3
The membrane-bound uPAR is illustrated in figure 1 A. uPAR is linked to the cell membrane by a glycosyl phosphatidylinositol (GPI)-anchor and binding of urokinase plasminogen activator (uPA) to uPAR, facilitates cleavage of the anchor and hence shedding of the receptor (Fig 1.). Once this anchor is cleaved the protein is released from the membrane and becomes soluble as illustrated in figure 1 B.
suPAR and its ligand are involved in numerous physiological and pathological pathways, which include the plasminogen activating pathway, regulation of pericellular proteolysis, modulation of cell adhesion, migration and proliferation through interactions with proteins present in the extracellular matrix. The involvement of the soluble form of the receptor in the inflammation process is well documented although the actual biological function of the molecule is still not clear. Studies suggest that suPAR is a regulator of uPAR/uPA actions through competitive inhibition of uPAR and several studies conclude that the cleaved receptor is a chemotatic agent promoting the immune response .
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