Abstract: TH-PO273

CD4 T Cells Activated by Ultrasound or Vagus Nerve Stimulation Protect Kidneys from Ischemia-Reperfusion Injury through β2 Adrenergic Receptor

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Inoue, Tsuyoshi, University of Virginia, Charlottesville, Virginia, United States
  • Abe, Chikara, Gifu University, Gifu, Japan
  • Huang, Liping, University of Virginia, Charlottesville, Virginia, United States
  • Rosin, Diane L., University of Virginia, Charlottesville, Virginia, United States
  • Guyenet, Patrice G., University of Virginia, Charlottesville, Virginia, United States
  • Okusa, Mark D., University of Virginia, Charlottesville, Virginia, United States
Background

We recently showed that prior ultrasound (US) treatment and vagus nerve stimulation (VNS) protect kidneys from ischemia-reperfusion injury (IRI) through the cholinergic anti-inflammatory pathway (CAP). Although β2 adrenergic receptor- positive CD4+ T cells are thought to be components of the CAP, they have yet to be tested in mediating the protective effect of CAP activation following IRI.

Methods

Kidney IRI (bilateral, 26 mins) was used as an acute kidney injury (AKI) model and IRI was performed 24 hr after US (bilateral, 2 mins) or VNS (left side, 5 Hz, 50 μA for 10 min) treatment. Kidney injury was evaluated 24 hr later using plasma creatinine (PCr), kidney Kim-1 mRNA expression and histology (H&E). CD4+ splenocytes (MACS-enriched) were isolated from donor mice and transferred i.v. to recipient mice. Butoxamine was used as a β2 adrenergic receptor antagonist, and salbutamol was used as a β2 adrenergic receptor agonist.

Results

When butoxamine (15 mg/kg) was administered 30 mins prior to US and VNS, the renal protective effect of US and VNS was abolished (PCr: 0.20 and 1.76 mg/dl (P<0.001) for vehicle+US and butoxamine+US, respectively, n=7). Salbutamol (15 mg/kg) administration 24 hr prior to IRI protected the kidney. Adoptive transfer of CD4+ splenocytes (1x105 cells) from US-treated or VNS-treated mice to recipient mice subjected to IRI provided greater protection than CD4+ splenocytes from mice who received sham US or sham VNS (PCr: 0.44 and 1.31 mg/dl (P<0.001) for VNS- and sham VNS-treated CD4+ splenocytes from spleen, respectively, n=9). In addition, the kidney was protected when salbutamol-treated CD4+ splenocytes were transferred 24 hr prior to IRI.

Conclusion

These data demonstrate that activation of CD4+ splenocytes through β2 adrenergic receptors is important for the protective effect of US and VNS in AKI.

Funding

  • NIDDK Support