PB0872 - Urokinase-plasminogen-activator receptor is dynamically expressed on differently aged monocytes

Background: Monocytes can be divided into three different subsets, classical monocytes (CM), intermediate monocytes (IM) and non-classical monocytes (NCM). CMs transform to NCMs in around 7 days, which results in altered functions of monocyte subsets. The urokinase-plasminogen-activator receptor (uPAR) is differently expressed on different monocyte subsets and has crucial functions in cell migration, thereby shaping the monocyte subsets.

Aims: In this project we want to investigate the role of uPAR in monocyte function.

Methods: Human monocytes were isolated from whole blood and kept for 8 days, we used flow cytometry to analyse uPAR expression changes. To investigate the role of uPAR in adhesion, we coated wells with vitronectin with and without uPAR inhibition. Monocytes were incubated for 1h under circular shear stress.
To study the transformation dynamics of monocytes, human volunteers received an in vivo leukocyte depletion at day 0. Every day blood samples were taken and analysed by flow cytometry to determine changes in uPAR expression.

Results: Our data revealed that uPAR has fundamental function in cell adhesion. Blocking uPAR on human monocytes leads to a significantly decreased adhesion. In addition, we observed a uPAR loss during the transformation of CM into NCM leading to the assumption, that matured NCMs are lacking uPAR. To obtain insights in monocytes transformation dynamics, NCM of human volunteers treated with an in vivo leukocyte depletion were analysed. We observed a significant increased uPAR expression in NCM after 8 days of treatment compared to uPAR expression at day 0. Here we hypothesize that an accelerated transformation of NCM from CM leads to a younger NCM population, characterized by an increased expression of uPAR on NCM.

Conclusion(s): We demonstrated that uPAR is dynamically expressed on human monocytes. In young NCM subsets uPAR is significantly increased. In contrast matured NCM express low amounts of uPAR.