Salt-sensitive increase in macrophages in the kidneys of dahl SS rats

Daniel J. Fehrenbach, Justine M. Abais-Battad, John Henry Dasinger, Hayley Lund, David L. Mattson

Research output: Contribution to journalArticle

Abstract

Studies of Dahl salt-sensitive (SS) rats have shown that renal CD3+ T cells and ED-1+ macrophages are involved in the development of salt-sensitive hypertension and renal damage. The present study demonstrated that the increase in renal immune cells, which accompanies renal hypertrophy and albuminuria in high-salt diet-fed Dahl SS rats, is absent in Sprague-Dawley and SSBN13 rats that are protected from the SS disease phenotype. Flow cytometric analysis demonstrated that >70% of the immune cells in the SS kidney are M1 macrophages. PCR profiling of renal myeloid cells showed a salt-induced upregulation in 9 of 84 genes related to Toll-like receptor signaling, with notable upregulation of the Toll-like receptor 4/CD14/MD2 complex. Because of the prominent increase in macrophages in the SS kidney, we used liposome-encapsulated clodronate (Clod) to deplete macrophages and assess their contribution to salt-sensitive hypertension and renal damage. Dahl SS animals were administered either Clod-con-taining liposomes (Clod-Lipo), Clod, or PBS-containing liposomes as a vehicle control. Clod-Lipo treatment depleted circulating and splenic macrophages by ~50%; however, contrary to our hypothesis, Clod-Lipo-treated animals developed an exacerbated salt-sensitive response with respect to blood pressure and albuminuria, which was accompanied by increased renal T and B cells. Interestingly, those treated with Clod also demonstrated an exacerbated phenotype, but it was less severe than Clod-Lipo-treated animals and independent of changes to the number of renal immune cells. Here, we have shown that renal macrophages in Dahl SS animals sustain a M1 proinflammatory phenotype in response to increased dietary salt and highlighted potential adverse effects of Clod-Lipo macrophage depletion.

Original languageEnglish (US)
Pages (from-to)F361-F374
JournalAmerican Journal of Physiology - Renal Physiology
Volume317
Issue number2
DOIs
StatePublished - Aug 2019
Externally publishedYes

Fingerprint

Inbred Dahl Rats
Clodronic Acid
Salts
Macrophages
Kidney
Liposomes
Renal Hypertension
Albuminuria
Phenotype
Up-Regulation
T-Lymphocytes
Toll-Like Receptor 4
Toll-Like Receptors
Myeloid Cells
Hypertrophy
Sprague Dawley Rats
B-Lymphocytes

Keywords

  • Clodronate
  • Hypertension
  • Liposome
  • Macrophage
  • Salt sensitive

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Fehrenbach, D. J., Abais-Battad, J. M., Dasinger, J. H., Lund, H., & Mattson, D. L. (2019). Salt-sensitive increase in macrophages in the kidneys of dahl SS rats. American Journal of Physiology - Renal Physiology, 317(2), F361-F374. https://doi.org/10.1152/ajprenal.00096.2019

Salt-sensitive increase in macrophages in the kidneys of dahl SS rats. / Fehrenbach, Daniel J.; Abais-Battad, Justine M.; Dasinger, John Henry; Lund, Hayley; Mattson, David L.

In: American Journal of Physiology - Renal Physiology, Vol. 317, No. 2, 08.2019, p. F361-F374.

Research output: Contribution to journalArticle

Fehrenbach, DJ, Abais-Battad, JM, Dasinger, JH, Lund, H & Mattson, DL 2019, 'Salt-sensitive increase in macrophages in the kidneys of dahl SS rats', American Journal of Physiology - Renal Physiology, vol. 317, no. 2, pp. F361-F374. https://doi.org/10.1152/ajprenal.00096.2019
Fehrenbach, Daniel J. ; Abais-Battad, Justine M. ; Dasinger, John Henry ; Lund, Hayley ; Mattson, David L. / Salt-sensitive increase in macrophages in the kidneys of dahl SS rats. In: American Journal of Physiology - Renal Physiology. 2019 ; Vol. 317, No. 2. pp. F361-F374.
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