Abstract: FR-PO1014

Adenosine Pathway Implication in M2 Macrophage Phenotype Switch in Deceased Renal Donors

Session Information

Category: Transplantation

  • 1701 Transplantation: Basic and Experimental

Authors

  • Diaz Encarnacion, Montserrat M., Fundación Pugvert, Barcelona, Spain
  • Guillen-gomez, Elena, Fundación Puigvert, Barcelona, Spain
  • Guirado, L., Fundació Puigvert, Barcelona, Spain
  • Ballarin, Jose, None, Barcelona, Spain
Background

A recent publication from our group shows that before kidney transplantation there is an activation and infiltration of immune cells in grafts from deceased donors. Adenosine levels increase during inflammation and hypoxia, principally through the hydrolysis of ATP, which is released after cell damage/death. This adenosine increment could initiate a macrophage phenotype shift from an ATP-driven pro-inflammatory environment to an anti-inflammatory and even pro-fibrotic milieu.

Methods

The aim of this study is to address the implication of purinome membrane elements in inflammation and fibrosis driven by macrophages in renal grafts.
Purinergic markers from pre-implantational renal allograft biopsies from living (LD) and deceased donors (DD) were quantified by qPCR and western-blot.

Results

Kidney samples from DD showed activation of both macrophage M1 inflammatory and M2 anti-inflammatory pathways evidenced by an increased expression of M1 and M2 markers. This result point to an early inflammatory response followed by activation of mechanisms for inflammation resolution. We found that expression of CNT2, a high-affinity Na+-dependent adenosine transporter, is decreased. This is consistent with the need to increase extracellular adenosine concentration by inhibiting its uptake, since the extracellular conversion to adenosine is also limited by the ecto-5'-nucleotidase CD73 inhibition. In addition, CNT2 correlated with the adenosine receptor A2a (A2AR), which suggests that extracellular adenosine would activate A2AR to trigger anti-inflammatory processes through cAMP increase. Western-blot results indicate an activation of A2AR-PKA-CREB pathway as well as an increase of the M2 macrophage marker CD163, in DD biopsies. Moreover A2AR expression correlates with pro-fibrotic markers such as α-SMA, fibronectin, vimentin and collagen.

Conclusion

Persistent inflammation in DD and M2 macrophage activation by extracellular adenosine even before implantation would contribute to the induction of pro-fibrotic processes in grafts from DD.