Interferon alpha-induced uPAR expression on monocytes as a potential source of increased soluble uPAR in patients...

The soluble urokinase plasminogen activator receptor (suPAR) has been shown to adequately predict the risk of organ damage development in patients with systemic lupus erythematosus (SLE). However, the cellular source and mechanism of increased circulating levels remain unknown. The cell-bound uPAR is expressed on various cell types and can be shed from the plasma membrane surface by proteases, resulting in the soluble form, suPAR. Herein, leukocyte uPAR expression and plasma suPAR levels were explored in unstimulated and cytokine-treated (tumor necrosis factor; TNF or interferon-α; IFN-α) blood from patients with SLE (n = 37) and healthy blood donors (HBD; n = 27). Unstimulated or cytokine-treated whole blood was thereafter used for analysis of cellular uPAR expression by flow cytometry, and plasma suPAR levels by enzyme-linked immunosorbent assay (ELISA). Monocytes and neutrophils had the most prominent uPAR expression and showed increased expression after TNF addition to the blood (p < 0.001). Addition of IFN-α resulted in increased uPAR expression only in patients (p < 0.05). No differences in uPAR expression were found depending on organ damage or other clinical variables. Nevertheless, suPAR levels were higher in patients with organ damage (p < 0.01). Unstimulated suPAR levels were correlated with monocyte uPAR expression in patient samples (rho = 0.4). As circulating suPAR levels can predict organ damage development in SLE, it is important to unravel its potential disease mediating effects as well as cellular sources. Results of this study suggest IFN-α as a regulator of uPAR expression in SLE and monocyte uPAR as an important source of plasma suPAR.