The chemokine receptor CX3CR1 reduces renal injury in mice with angiotensin II induced hypertension
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The chemokine receptor CX3CR1 reduces renal injury in mice with angiotensin II induced hypertension. / Ahadzadeh, Erfan; Rosendahl, Alva; Czesla, Daniel; Steffens, Paula; Prüßner, Lennard; Meyer-Schwesinger, Catherine; Wanner, Nicola; Paust, Hans Joachim; Huber, Tobias B; Stahl, Rolf Ak; Wiech, Thorsten; Kurts, Christian; Seniuk, Anika; Ehmke, Heimo; Wenzel, Ulrich O.
in: AM J PHYSIOL-RENAL, Jahrgang 315, Nr. 6, 01.12.2018, S. F1526-F1535.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The chemokine receptor CX3CR1 reduces renal injury in mice with angiotensin II induced hypertension
AU - Ahadzadeh, Erfan
AU - Rosendahl, Alva
AU - Czesla, Daniel
AU - Steffens, Paula
AU - Prüßner, Lennard
AU - Meyer-Schwesinger, Catherine
AU - Wanner, Nicola
AU - Paust, Hans Joachim
AU - Huber, Tobias B
AU - Stahl, Rolf Ak
AU - Wiech, Thorsten
AU - Kurts, Christian
AU - Seniuk, Anika
AU - Ehmke, Heimo
AU - Wenzel, Ulrich O
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The role of CX3CR1, also known as fractalkine receptor, in hypertension is unknown. The present study determined the role of the fractalkine receptor CX3CR1 in hypertensive renal and cardiac injury. Expression of CX3CR1 was determined using CX3CR1GFP/+ mice that express a green fluorescent protein (GFP) reporter in CX3CR1+ cells. FACS analysis of leukocytes isolated from the kidney showed that 34% of CD45+ cells expressed CX3CR1. Dendritic cells were the majority of positive cells (67%) followed by macrophages (10%), NK cells (6%), and T cells (10%). With the use of confocal microscopy, the receptor was detected in the kidney only on infiltrating cells but not on resident renal cells. To evaluate the role of CX3CR1 in hypertensive end-organ injury, an aggravated model of hypertension was used. Unilateral nephrectomy was performed followed by infusion of angiotensin II (ANG II, 1.5 ng·g-1·min-1) and a high-salt diet in wild-type ( n = 15) and CX3CR1-deficient mice ( n = 18). CX3CR1 deficiency reduced the number of renal dendritic cells and increased the numbers of renal CD11b/F4/80+ macrophages and CD11b/Ly6G+ neutrophils in ANG II-infused mice. Surprisingly, CX3CR1-deficient mice exhibited increased albuminuria, glomerular injury, and reduced podocyte density in spite of similar levels of arterial hypertension. In contrast, cardiac damage as assessed by increased heart weight, cardiac fibrosis, and expression of fetal genes, and matrix components were not different between both genotypes. Our findings suggest that CX3CR1 exerts protective properties by modulating the invasion of inflammatory cells in hypertensive renal injury. CX3CR1 inhibition should be avoided in hypertension because it may promote hypertensive renal injury.
AB - The role of CX3CR1, also known as fractalkine receptor, in hypertension is unknown. The present study determined the role of the fractalkine receptor CX3CR1 in hypertensive renal and cardiac injury. Expression of CX3CR1 was determined using CX3CR1GFP/+ mice that express a green fluorescent protein (GFP) reporter in CX3CR1+ cells. FACS analysis of leukocytes isolated from the kidney showed that 34% of CD45+ cells expressed CX3CR1. Dendritic cells were the majority of positive cells (67%) followed by macrophages (10%), NK cells (6%), and T cells (10%). With the use of confocal microscopy, the receptor was detected in the kidney only on infiltrating cells but not on resident renal cells. To evaluate the role of CX3CR1 in hypertensive end-organ injury, an aggravated model of hypertension was used. Unilateral nephrectomy was performed followed by infusion of angiotensin II (ANG II, 1.5 ng·g-1·min-1) and a high-salt diet in wild-type ( n = 15) and CX3CR1-deficient mice ( n = 18). CX3CR1 deficiency reduced the number of renal dendritic cells and increased the numbers of renal CD11b/F4/80+ macrophages and CD11b/Ly6G+ neutrophils in ANG II-infused mice. Surprisingly, CX3CR1-deficient mice exhibited increased albuminuria, glomerular injury, and reduced podocyte density in spite of similar levels of arterial hypertension. In contrast, cardiac damage as assessed by increased heart weight, cardiac fibrosis, and expression of fetal genes, and matrix components were not different between both genotypes. Our findings suggest that CX3CR1 exerts protective properties by modulating the invasion of inflammatory cells in hypertensive renal injury. CX3CR1 inhibition should be avoided in hypertension because it may promote hypertensive renal injury.
KW - Journal Article
U2 - 10.1152/ajprenal.00149.2018
DO - 10.1152/ajprenal.00149.2018
M3 - SCORING: Journal article
C2 - 30207169
VL - 315
SP - F1526-F1535
JO - AM J PHYSIOL-RENAL
JF - AM J PHYSIOL-RENAL
SN - 1931-857X
IS - 6
ER -
