suPAR and its ligand are involved in numerous physiological and pathological pathways, including the plasminogen activating pathway, regulation of pericellular proteolysis, modulation of cell adhesion, migration, and proliferation through interactions with proteins present in the extracellular matrix.4
The soluble form of the receptor in the inflammation process is well described. Studies suggest that suPAR is a regulator of uPAR/uPA actions through competitive inhibition of uPAR. Several studies conclude that the cleaved receptor is a chemotactic agent promoting the immune response.3
“It is essential to have the help of biomarkers, such as suPAR, which can support the discharge decision”
Juan González del Castillo, Dr PhD, Hospital Clínico San Carlos, Spain
suPAR News Vol. 1, April 2019
In April 2006, the crystal structure of suPAR was published in Science. The three-domain structure was shown to differentially rotate around its main axis to accommodate several complex ligands1. Due to this ability to change conformation, suPAR demonstrates a highly variable binding pocket, believed to explain its immense value in various biological functions.
uPAR is expressed on the surface of immune cells, particularly monocytes and activated T-cells. It is involved in several immune functions, including migration, adhesion, angiogenesis, fibrinolysis, and cell proliferation. The shedding of uPAR from the cell surface generates soluble uPAR (suPAR)4.
uPAR has been shown to promote invasion by neoplastic or inflammatory cells by focusing proteolysis of urokinase to the cell surface. In pathologic conditions, suPAR is released and activate cell receptors to promote chemotaxis and immune response.
It has also been published that no genetic polymorphisms exist, causing humans to naturally express high levels of suPAR2. This indicates that elevated concentrations of suPAR can be ascribed to immune activation or immune response to a specific challenge. Further scientific data strengthen the conclusion that – independent of infection type – elevated blood levels of suPAR carry a strong negative prognostic value for the respective disease condition.
1: Xu X et al., Crystal structure of the urokinase receptor in a ligand-free form J Mol Biol. 2012 Mar 9;416(5):629-41.
2: Schneider UV et al., The prognostic value of the suPARnostic ELISA in HIV-1 infected individuals is not affected by uPAR promoterpolymorphisms, BMC Infect Dis. 2007 Nov 16;7:134
3. Huai Q, et al. Structure of human urokinase plasminogen activator in complex with its receptor, Science. 2006 Feb 3;311(5761):656-9.
4. Thunø M et al., suPAR: the molecular crystal ball, Dis Markers. 2009;27(3):157-72.