Kidney Week

Abstract: SA-PO1077

Renal Dendritic Cells from Hypertensive Mice Transferred Hypertension and Modified Renal Sodium Handling

Session Information

• Hypertension: Basic and Experimental - Treatment and Mechanisms
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

• 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

• Araos, Patricio A., Millennium Institute on Immunology and Immunotherapy, Santiago, Chile

Patricio A. Araos,

• Prado, Carolina E., Fundacion Ciencia y Vida, Santiago, Chile

Carolina E. Prado,

• Salas-Huenuleo, Edison Sebastián, Depto. de Química toxicológica y Farmacológica, Facultad de Cs. Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile

Edison Sebastián Salas-Huenuleo,

• Kogan, Marcelo, Depto. de Química toxicológica y Farmacológica, Facultad de Cs. Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile

Marcelo Kogan,

• Pacheco, Rodrigo, Fundacion Ciencia y Vida, Santiago, Chile

Rodrigo Pacheco,

• Michea, Luis F., Millennium Institute on Immunology and Immunotherapy, Santiago, Chile

Luis F. Michea,

Background

High Angiotensin II (AngII) induce hypertension (HT). Previously, using genetically modified mice that allowed the systemic ablation of Dendritic Cells (DCs), we observed that DCs are necessary for the development of HT.The kidney is a tissue rich in DCs, which are present in the interstitial space. We hypothesized that renal DCs have pro-hypertensive properties that are acquired after HT.

Methods

In this study, we evaluated if renal DCs from hypertensive mice (AngII infusion, osmotic minipump, 1.042 μg/Kg/min, 14d) can transfer HT. We compared the transfer of renal DCs and splenic DCs from control (WT) and hypertensive mice (CD11c⁺ cells, magnetic beads isolation). Isolated DCs from control and hypertensive mice were characterized (CD86, CD80, MHC-II and CX₃CR₁, flow cytometry). We monitoring blood pressure (BP, tail cuff method), and tracked DCs location after transferring (tail vein injection) by labeling DCs with a DiR dye (In vivo FX Pro system, Bruker). To evaluate the effect of DCs transferring on renal Na⁺ handling, we challenged recipient mice with the injection of isotonic saline solution (saline test, 10% of BW, i.p. injection) and measured 4h-natriuresis 24h post-DCs transfer.

Results

Renal DCs obtained from hypertensive mice showed increased abundance of CD80, CD86, MHC-II, and CX₃CR₁ (MFI fold of induction: 1.6±0.2; 1.6±0.4; 1.4±0.3 and 3.2±0.8 respectively p<0.05 vs control; n=4-8).Transfer of renal DCs from hypertensive mice transiently increased BP (basal=102.5±4.4; day 1=123.3±4.4; mmHg; n=5, p< 0,001 vs basal). In contrast, transfer of splenic DCs did not modify BP. Renal DCs showed renal-preferential location 24 hours post injection, irrespective of the origin (control or hypertensive kidney). Recipients of hypertensive renal DCs showed decreased renal sodium excretion (basal urinary Na⁺ excretion=10.2±1.9 vs. 8.2±0.8 µEq/BW/4h 1 day after transfer; p<0,05 n=5).

Conclusion

Renal, but not splenic, hypertensive DCs presented a preferential homing to kidney, transferred hypertension and transiently reduced natriuresis.These results suggest that renal DCs have a pro-hypertensive phenotype, acquired after the development of hypertension, which confers the ability of modulating sodium renal handling.
FONDECYT1130550 and 1171869, IMII P09-016-F,BECA CONICYT 21130482

Funding

• Government Support - Non-U.S.