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Renal denervation prevents dendritic cell activation and renal T cell activation in mice in angiotensin II‐induced hypertension (1082.4)
Author(s) -
Xiao Liang,
Kirabo Annet,
Wu Jing,
Harrison David
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1082.4
Subject(s) - angiotensin ii , medicine , endocrinology , kidney , cd80 , renin–angiotensin system , dendritic cell , denervation , losartan , chemistry , cd40 , immunology , immune system , receptor , blood pressure , cytotoxic t cell , in vitro , biochemistry
Hypertension is associated with increased sympathetic outflow and subsequent activation of adaptive immunity. We hypothesized that renal sympathetic nerves activate dendritic cells, and that these in turn cause T cells to proliferate and accumulate in the kidney. To test this, we performed bilateral renal denervation (RDN) in C57BL/6 mice by applying phenol to the renal artery and cutting large visible nerves. One week later, mice received angiotensin II (490 ng/kg/min) subcutaneously for 14 days. RDN lowered the hypertensive response to angiotensin II (130±3 vs. 161±3 mmHg, p<0.001) as measured by telemetry. By flow cytometry, we found that angiotensin II increased expression of surface markers CD80 and CD86 on dendritic cells of the kidney by 2 to 3‐fold and that this is significantly attenuated by RDN. RDN also reduced accumulation of total T cells and CD44 hi (memory) T cells in the kidney (See table). Moreover, angiotensin II increased IL‐1α, IL‐1β, and IL‐6 production from splenic dendritic cells by 4 to 6‐fold, and RDN eliminated this. In other studies, we found that adoptive transfer of dendritic cells from angiotensin II infused mice augmented the hypertensive response to low dose angiotensin II (140 ng/kg/min), while transfer of dendritic cells from mice that had received angiotensin II after RDN had no effect on the recipient mouse (systolic 156±10 vs 135±9 mmHg, p<0.05). These results indicate that renal sympathetic nerves cause dendritic cell activation, and that dendritic cells play a critical role in the genesis of hypertension.Sham Angiotensin RDN+Angiotensin Inflammatory cells in kidney (×10 4 per kidney): Leukocytes (CD45+) 10.5±1.6 16.8±3.0* 8.9±1.0â€T cells (CD3+) 1.7±0.3 3.9±0.8* 1.7±0.2â€Activated dendritic cells(×10 3 per kidney): CD80+ 1.09±0.19 2.90±0.39* 2.00±0.42â€CD86+ 0.47±0.05 0.87±0.12* 0.59±0.12â€Cytokines production in DCs (ng per 10 6 cells): IL‐1α 0.76±0.10 5.04±2.20* 0.59±0.18â€IL‐1β 3.18±0.32 23.99±13.59* 2.75±0.84â€IL‐6 1.05±0.20 12.36±7.45* 1.02±0.34â€*p<0.05 vs. sham; †p<0.05 vs. ANG