TY - GEN
T1 - Neutrophil Depletion Influences Renal Outcomes in Male Mice with Chronic Angiotensin II Infusion
AU - Smith, Kelsie
AU - Harr, Hannah Ter
AU - Browning, Brittney
AU - Gigliotti, Joseph C.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Hypertension is the leading cause of morbidity and mortality worldwide; yet the exact cause for many cases remain unknown. Recent research has highlighted the significance of the immune system in the development and progression of HTN in animal models. Much of this research has focused on classical immune pathways involving antigen presenting cells and subsequent activation of the adaptive immune response (primarily CD8+ T-cells). These activated lymphocytes then support the development of HTN by mediating end-organ damage in organs tasked with regulating blood pressure and extracellular volume (such as the kidneys). In the current study, we set out to determine the role of neutrophils in a murine model of HTN – the chronic angiotensin II (AngII) infusion model. All animal experiments were performed following animal protocols approved by the Liberty University IACUC and conform to the FASEB Statement of Principles for the use of animals in research and education. Baseline blood pressure was recorded in male C57Bl/6 mice (N=10) for 3 weeks using the CODA-8 tail cuff volume pressure recording system. Neutrophil depletion was accomplished via intraperitoneal injections of a monoclonal anti-Ly6G antibody (1A8, n=5), or IgG control (2A3, n=5) every 48 hours (250μg/mouse). 18 hours following the first antibody injection, a mini-osmotic pump was implanted into the rear flank delivering 500ng/kg*min AngII. 3 days after pump implantation, blood pressure readings resumed and continued for 14 days. After 14 days, mice were individually housed in metabolic cages and urine was collected for quantification of albuminuria. Renal blood flow was estimated in anesthetized mice using contrast-enhanced ultrasonography. Following renal blood flow estimation, mice were euthanized and blood, kidney, and spleens collected for determination of leukocyte content by flow cytometry. All data were analyzed using general linear models procedures in SPSS. Significant differences in blood pressure were observed periodically during the 14 days of AngII infusion (P≤0.05 for days 8, 12, and 14); however, the overall effect of treatment (1A8 vs. 2A3) did not reach statistical significance (P
AB - Hypertension is the leading cause of morbidity and mortality worldwide; yet the exact cause for many cases remain unknown. Recent research has highlighted the significance of the immune system in the development and progression of HTN in animal models. Much of this research has focused on classical immune pathways involving antigen presenting cells and subsequent activation of the adaptive immune response (primarily CD8+ T-cells). These activated lymphocytes then support the development of HTN by mediating end-organ damage in organs tasked with regulating blood pressure and extracellular volume (such as the kidneys). In the current study, we set out to determine the role of neutrophils in a murine model of HTN – the chronic angiotensin II (AngII) infusion model. All animal experiments were performed following animal protocols approved by the Liberty University IACUC and conform to the FASEB Statement of Principles for the use of animals in research and education. Baseline blood pressure was recorded in male C57Bl/6 mice (N=10) for 3 weeks using the CODA-8 tail cuff volume pressure recording system. Neutrophil depletion was accomplished via intraperitoneal injections of a monoclonal anti-Ly6G antibody (1A8, n=5), or IgG control (2A3, n=5) every 48 hours (250μg/mouse). 18 hours following the first antibody injection, a mini-osmotic pump was implanted into the rear flank delivering 500ng/kg*min AngII. 3 days after pump implantation, blood pressure readings resumed and continued for 14 days. After 14 days, mice were individually housed in metabolic cages and urine was collected for quantification of albuminuria. Renal blood flow was estimated in anesthetized mice using contrast-enhanced ultrasonography. Following renal blood flow estimation, mice were euthanized and blood, kidney, and spleens collected for determination of leukocyte content by flow cytometry. All data were analyzed using general linear models procedures in SPSS. Significant differences in blood pressure were observed periodically during the 14 days of AngII infusion (P≤0.05 for days 8, 12, and 14); however, the overall effect of treatment (1A8 vs. 2A3) did not reach statistical significance (P
M3 - Other contribution
T3 - Faculty Publications and Presentations
ER -