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Abstract: FR-PO967

Kidney Injury Enhances Renal Granulocyte-Colony Stimulating Factor Expression, Granulopoiesis, and Human Neutrophilic Granulocyte Proteinase 3 Receptor CD177 Expression

Session Information

Category: Pathology and Lab Medicine

  • 1601 Pathology and Lab Medicine: Basic

Authors

  • Volkmann, Julia, Hannover Medical School, Hannover, Germany
  • Schmitz, Jessica, Hannover Medical School, Hannover, Germany
  • Helmke, Alexandra, Hannover Medical School, Hannover, Germany
  • Sen, Payel, Medizinische Hochschule Hannover, Hannover, Germany
  • Braesen, Jan H., Medizinische Hochschule Hannover, Hannover, Germany
  • Bernhardt, Wanja, Heidering Dialysis clinic, Hannover, Germany
  • Immenschuh, Stephan, Hannover Medical School, Hannover, Germany
  • Gwinner, Wilfried, Medical School Hanover, Hannover, Germany
  • Schmitt, Roland, Medizinische Hochschule Hannover, Hannover, Germany
  • Haller, Hermann G., Hannover Medical School, Hannover, Germany
  • Von Vietinghoff, Sibylle, Hannover Medical School, Hannover, Germany
Background

Acute kidney injury causes significant systemic adverse events beyond retention of uremic waste and volume expansion, mechanisms of which are incompletely understood. Neutrophilic granulocytes, the most abundant human blood leukocytes, are characterized by a high turnover rate. They are chiefly controlled by granulocyte colony stimulating factor (G-CSF), which can be produced by diverse cell types. The impact of kidney injury on G-CSF production and granulopoiesis has not been determined.

Methods

Renal G-CSF expression in murine experimental kidney injury and after human kidney transplantation was assessed by immunostaining and qPCR. Neutrophils were characterized by flow cytometry in mice with experimental kidney injury, patients with chronic kidney disease, before and after kidney transplantation and in healthy controls. Human cell culture was employed for mechanistic experiments.

Results

In murine experimental ischemia reperfusion injury and unilateral ureteral obstruction, renal G-CSF mRNA and protein increased and characteristics of emergency granulopoiesis developed in bone marrow and blood. In humans, G-CSF and kidney transplantation similarly transiently elevated human neutrophil expression of CD177, a highly G-CSF responsive neutrophil gene. In kidney graft recipients, the rise in CD177 correlated with renal tubular G-CSF expression. In contrast, CD177 was unaltered in patients with chronic renal impairment independent of renal replacement therapy. As possible underlying mechanisms, hypoxia and proinflammatory cytokine interleukin 17A enhanced G-CSF expression in human renal tubular epithelial cells, while complement activation promoted G-CSF in endothelium.

Conclusion

Our data demonstrate induction of renal G-CSF and modulation of granulopoiesis after kidney injury. They delineate differential G-CSF regulation in renal epithelium and endothelium. Altered granulopoiesis may contribute to the distant effects and possibly prognostic role of kidney injury.

Funding

  • Government Support - Non-U.S.