Kidney Week

Abstract: SA-PO564

Dynamic regulation of macrophage subpopulations in mouse models of kidney injury

Session Information

• Glomerular Diseases: Fibrosis, Extracellular Matrix
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Nordlohne, Johannes, Bayer AG, Wuppertal, Germany

Johannes Nordlohne,

• Hulsmann, Ilona, Bayer AG, Wuppertal, Germany

Ilona Hulsmann,

• Schwafertz, Svenja, Bayer AG, Wuppertal, Germany

Svenja Schwafertz,

• Eitner, Frank, Bayer AG, Wuppertal, Germany

Frank Eitner,

• Becker, Michael S., Bayer, Wuppertal, Germany

Michael S. Becker,

Background

Macrophages are key drivers of kidney fibrosis and therapeutic efforts have been made to manipulate immuno-regulatory macrophage functions in vivo. However, the moderate success of these approaches might be explained by a poor understanding of macrophage kinetics, functional relevance of distinct macrophage subpopulations, and model specific differences.

Methods

We analyzed kidney macrophages in healthy mice and two models of kidney damage, unilateral ureteral obstruction (UUO) and ischemia reperfusion injury (IRI) by a flow cytometry strategy. We identified five kidney macrophage subpopulations with distinct expression of myeloid markers CD11b and CD11c, based on a strategy by Kawakami et al. (2013; J Immunol.).

Results

All macrophage populations, particularly CD11b^highCD11c^high macrophages, were increased in diseased mice compared to healthy mice. Model specific differences revealed 8-fold more blood-derived monocytes (CD11b^highCD11c^low) after eight days of UUO than after six days of IRI (840 vs 110 cells/mg kidney). Surface markers MHCII and CD206 allowed further distinction between more pro-inflammatory “M1”- and immuno-regulatory “M2”-like macrophages, illustrating dynamic contribution of each of the five macrophage populations. Treatment with the VEGF receptor tyrosine kinase inhibitor tivozanib effectively reduced total numbers of MHCII-positive and CD11b^highCD11c^high macrophages after eight days of UUO.

Conclusion

In conclusion, we were able to reveal kinetic and model specific changes in kidney macrophage subpopulations occurring under damage. Being able to monitor and understand the dynamics of different macrophage subsets within diseased organs could help in finding new therapeutic angles.

Funding

• Commercial Support – Bayer AG