Abstract: TH-OR015

Parabiosis Reveals Renal Resident Leukocytes in Quiescence and AKI

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Lever, Jeremie M., University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Boddu, Ravindra, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Adedoyin, Oreoluwa O., University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Yang, Zhengqin, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Guo, Lingling, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Traylor, Amie, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Joseph, Reny, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • George, James F, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Agarwal, Anupam, University of Alabama at Birmingham , Birmingham, Alabama, United States
Background

Inflammation drives damage and promotes tissue regeneration in AKI, but the origin of inflammatory cells found in renal tissue (infiltrative versus tissue-resident) has remained elusive. In this study, we developed a novel model of AKI in parabiosis chimeras to study exchange of inflammatory cells with the circulation. Our goal was to discern which renal leukocyte populations are tissue-resident and how this may change in the setting of injury-induced inflammation.

Methods

Parabiosis was established between C57BL/6J adult congenic mice with differing CD45 allotypes, allowing identification of cells from each individual. After 28d, chimeras were subject to 30m of renal ischemia-reperfusion injury (IRI) or sham surgery and harvested at 24 and 72h. Kidney, peripheral blood, and spleen were analyzed by multicolor flow cytometry.

Results

After 28d of parabiosis, chimerism for intrarenal neutrophils was 24.2% (95% CI, 14.2 to 34.2). In contrast, F4/80HiCD11bLowCX3CR1HiCD11c+ macrophages, CD3+CD4-CD8- T lymphocytes, and NK1.1+CD3+ NKT cells in the kidney demonstrated low exchange with the blood, with chimerism equal to 2.4% (95% CI, 1.0 to 3.8%; p = 0.002 compared with blood), 2.3% (95% CI, 0.6 to 4.1%; p = 0.02), and 2.3% (95% CI, 0.7 to 3.9%; p = 0.002), respectively in uninjured kidneys. In injured kidneys, a trend toward chimeric CD45.1+ leukocyte infiltration was observed relative to sham control (6.6 x 105 ± 1.1 x 104 vs 1.8 x 105 ± 8.4 x 104 cells/g tissue, p = 0.10, n = 3 pairs, 24h after injury). However, absolute numbers of chimeric F4/80HiCD11bLowCX3CR1HiCD11c+ macrophages were not different, indicating bone marrow precursors from the peripheral blood do not supplement expansion of this population, even in the setting of acute inflammation.

Conclusion

Certain renal leukocyte populations exhibit low or no exchange with the peripheral blood, indicating they are long-lived or undergo self-renewal in situ. Kidney resident macrophages do not appear to be supplemented by infiltrating cells during acute inflammation. These findings may be important in targeting inflammation after AKI with small molecule drugs or development of cell-based therapeutics.

Funding

  • NIDDK Support