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The chemokine receptor CX3CR1 reduces renal injury in mice with angiotensin II-induced hypertension
- Source :
- American Journal of Physiology-Renal Physiology. 315:F1526-F1535
- Publication Year :
- 2018
- Publisher :
- American Physiological Society, 2018.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Chemokine
biology
Physiology
business.industry
030204 cardiovascular system & hematology
Angiotensin II
Podocyte
03 medical and health sciences
Chemokine receptor
030104 developmental biology
0302 clinical medicine
Endocrinology
medicine.anatomical_structure
Renal injury
Internal medicine
CX3CR1
medicine
Albuminuria
biology.protein
medicine.symptom
Receptor
business
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 315
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi...........82d278ddbb31833e4e5e0c728f86c886