, Volume 33, Issue 1, pp 1–9 | Cite as

Release of the Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) by Activated Neutrophils in Rheumatoid Arthritis



Soluble form of the urokinase-type plasminogen activator receptor (suPAR) is markedly increased in biological fluids during different inflammatory conditions. It has previously been observed that the highest suPAR concentrations in inflammatory exudates tend to be associated with the presence of high number of neutrophils. Guided by this observation and our recent finding that activated neutrophils release suPAR we investigated whether neutrophils can be a source of suPAR during the inflammatory response in vivo. To address this question we conducted the comparative analysis of neutrophils isolated from the paired samples of synovial fluid (SF) and peripheral blood (PB) of rheumatoid arthritis patients. Freshly isolated SF neutrophils released significantly (p < 0.01) higher amounts of suPAR compared with PB neutrophils. We demonstrated that neutrophils from both sources release predominantly the truncated D2D3 form of suPAR. Migration of formyl peptide receptor-like 1 (FPRL1)-transfected human embryonic kidney (HEK) 293 cells toward the supernatants harvested from in vitro cultured SF neutrophils was significantly diminished when D2D3 form of suPAR was immunodepleted from the supernatants. Taken together, these data demonstrate that neutrophils, first, contribute to or are responsible for the generation of the increased suPAR levels during the inflammatory response and, second, release the chemotactically active form of suPAR that might be involved in the recruitment of formyl peptide receptors-expressing leukocytes into the inflamed tissues.


urokinase receptor soluble form neutrophils synovial fluids formyl peptide receptors 



peripheral blood


synovial fluid


enzyme-linked immunosorbent assay


Hank’s balanced salt solution


phosphate-buffered saline


urokinase-type plasminoden activator receptor


soluble uPAR


formyl peptide receptor-like-1



We are grateful to Dr. J. M. Wang (National Cancer Institute at Frederick, Frederick, USA) and Dr. P. M. Murphy (National Institute of Allergy and Infectious Diseases, NIH, Bethesda, USA) for providing FPRL1/293 cells. We also wish to thank Dr. T. Arefyeva (Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia) for her help in flow cytometry analysis. This work was supported by CRDF grant №RB1–2454-MO-02.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Biological and Medical Chemistry, Faculty of Fundamental MedicineMoscow State UniversityMoscowRussia
  2. 2.Department of Biochemistry, Institute of Experimental CardiologyCardiology Research CenterMoscowRussia

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