Ultrasound modulates the splenic neuroimmune axis in attenuating AKI

Joseph C. Gigliotti, Liping Huang, Amandeep Bajwa, Hong Ye, Eric H. Mace, John A. Hossack, Kambiz Kalantari, Tsuyoshi Inoue, Diane L. Rosin, Mark D. Okusa

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Abstract

We showed previously that prior exposure to a modified ultrasound regimen prevents kidney ischemiareperfusion injury (IRI) likely via the splenic cholinergic anti-inflammatory pathway (CAP) and a7 nicotinic acetylcholine receptors (α7nAChR). However, it is unclear how ultrasound stimulates the splenic CAP. Further investigating the role of the spleen in ischemic injury, we found that prior splenectomy (-7d) or chemical sympathectomy of the spleen with 6-hydroxydopamine (6OHDA; -14d) exacerbated injury after subthreshold (24-minute ischemia) IRI. 6-OHDA-induced splenic denervation also prevented ultrasoundinduced protection of kidneys from moderate (26-minute ischemia) IRI. Ultrasound-induced protection required hematopoietic but not parenchymal α7nAChRs, as shown by experiments in bone marrow chimeras generated with wild-type and α7nAChR-/- mice.Ultrasound protection was associated with reduced expression of circulating and kidney-derived cytokines. However, splenocytes isolated from mice 24 hours after ultrasound treatment released more IL-6 ex vivo in response to LPS than splenocytes from sham mice. Adoptive transfer of splenocytes from ultrasound-treated (but not sham) mice to naïve mice was sufficient to protect kidneys of recipient mice from IRI. Ultrasound treatment 24 hours before cecal ligation puncture-induced sepsis was effective in reducing plasma creatinine in this model of AKI. Thus, splenocytes of ultrasound-treated mice are capable of modulating IRI in vivo, supporting our ongoing hypothesis that a modified ultrasound regimen has therapeutic potential for AKI and other inflammatory conditions.

Original languageEnglish (US)
Pages (from-to)2470-2481
Number of pages12
JournalJournal of the American Society of Nephrology
Volume26
Issue number10
DOIs
StatePublished - Oct 1 2015

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Wounds and Injuries
Kidney
Oxidopamine
Cholinergic Agents
Anti-Inflammatory Agents
Spleen
Ischemia
Chemical Sympathectomy
Adoptive Transfer
Nicotinic Receptors
Denervation
Splenectomy
Punctures
Ligation
Interleukin-6
Creatinine
Sepsis
Therapeutics
Bone Marrow
Cytokines

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Gigliotti, J. C., Huang, L., Bajwa, A., Ye, H., Mace, E. H., Hossack, J. A., ... Okusa, M. D. (2015). Ultrasound modulates the splenic neuroimmune axis in attenuating AKI. Journal of the American Society of Nephrology, 26(10), 2470-2481. https://doi.org/10.1681/ASN.2014080769

Ultrasound modulates the splenic neuroimmune axis in attenuating AKI. / Gigliotti, Joseph C.; Huang, Liping; Bajwa, Amandeep; Ye, Hong; Mace, Eric H.; Hossack, John A.; Kalantari, Kambiz; Inoue, Tsuyoshi; Rosin, Diane L.; Okusa, Mark D.

In: Journal of the American Society of Nephrology, Vol. 26, No. 10, 01.10.2015, p. 2470-2481.

Research output: Contribution to journalArticle

Gigliotti, JC, Huang, L, Bajwa, A, Ye, H, Mace, EH, Hossack, JA, Kalantari, K, Inoue, T, Rosin, DL & Okusa, MD 2015, 'Ultrasound modulates the splenic neuroimmune axis in attenuating AKI', Journal of the American Society of Nephrology, vol. 26, no. 10, pp. 2470-2481. https://doi.org/10.1681/ASN.2014080769
Gigliotti, Joseph C. ; Huang, Liping ; Bajwa, Amandeep ; Ye, Hong ; Mace, Eric H. ; Hossack, John A. ; Kalantari, Kambiz ; Inoue, Tsuyoshi ; Rosin, Diane L. ; Okusa, Mark D. / Ultrasound modulates the splenic neuroimmune axis in attenuating AKI. In: Journal of the American Society of Nephrology. 2015 ; Vol. 26, No. 10. pp. 2470-2481.
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