Nicotine Mediates CD161a+ Renal Macrophage Infiltration and Premature Hypertension in the Spontaneously Hypertensive Rat

Sailesh C Harwani; Jason Ratcliff; Fayyaz S Sutterwala; Zuhair K Ballas; David K Meyerholz; Mark W Chapleau; Francois M Abboud

doi:10.1161/CIRCRESAHA.116.309402

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Nicotine Mediates CD161a+ Renal Macrophage Infiltration and Premature Hypertension in the Spontaneously Hypertensive Rat

Journal article

Open access

Peer reviewed

Nicotine Mediates CD161a+ Renal Macrophage Infiltration and Premature Hypertension in the Spontaneously Hypertensive Rat

Sailesh C Harwani, Jason Ratcliff, Fayyaz S Sutterwala, Zuhair K Ballas, David K Meyerholz, Mark W Chapleau and Francois M Abboud

Circulation research, Vol.119(10), pp.1101-1115

10/28/2016

DOI: 10.1161/CIRCRESAHA.116.309402

PMCID: PMC5085865

PMID: 27660287

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https://doi.org/10.1161/CIRCRESAHA.116.309402View

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Abstract

Renal inflammation contributes to the pathophysiology of hypertension. CD161a immune cells are dominant in the (SHR) spontaneously hypertensive rat and expand in response to nicotinic cholinergic activation. We aimed to phenotype CD161a immune cells in prehypertensive SHR after cholinergic activation with nicotine and determine if these cells are involved in renal inflammation and the development of hypertension. Studies used young SHR and WKY (Wistar-Kyoto) rats. Splenocytes and bone marrow cells were exposed to nicotine ex vivo, and nicotine was infused in vivo. Blood pressures, kidney, serum, and urine were obtained. Flow cytometry, Luminex/ELISA, immunohistochemistry, confocal microscopy, and Western blot were used. Nicotinic cholinergic activation induced proliferation of CD161a /CD68 macrophages in SHR-derived splenocytes, their renal infiltration, and premature hypertension in SHR. These changes were associated with increased renal expression of MCP-1 (monocyte chemoattractant protein-1) and VLA-4 (very-late antigen-4). LLT1 (lectin-like transcript 1), the ligand for CD161a, was overexpressed in SHR kidney, whereas vascular cellular and intracellular adhesion molecules were similar to those in WKY. Inflammatory cytokines were elevated in SHR kidney and urine after nicotine infusion. Nicotine-mediated renal macrophage infiltration/inflammation was enhanced in denervated kidneys, not explained by angiotensin II levels or expression of angiotensin type-1/2 receptors. Moreover, expression of the anti-inflammatory α7-nAChR (α7-nicotinic acetylcholine receptor) was similar in young SHR and WKY rats. A novel, inherited nicotinic cholinergic inflammatory effect exists in young SHR, measured by expansion of CD161a /CD68 macrophages. This leads to renal inflammation and premature hypertension, which may be partially explained by increased renal expression of LLT-1, MCP-1, and VLA-4.

Kidney - pathology

Male

Antigens, CD - analysis

Receptor, Angiotensin, Type 1 - genetics

Nephritis - chemically induced

Hypertension - genetics

Cytokines - genetics

Prehypertension - genetics

NK Cell Lectin-Like Receptor Subfamily B - analysis

Macrophages - classification

Macrophages - pathology

Nephritis - physiopathology

Rats

alpha7 Nicotinic Acetylcholine Receptor - genetics

Hypertension, Renal - pathology

Hypertension - pathology

Hypertension - metabolism

Cell Movement - drug effects

Age of Onset

Antigens, Differentiation, Myelomonocytic - analysis

Chemokine CCL2 - biosynthesis

Kidney - innervation

Lectins - genetics

Hypertension, Renal - genetics

alpha7 Nicotinic Acetylcholine Receptor - biosynthesis

Prehypertension - etiology

Rats, Inbred WKY

Hypertension, Renal - metabolism

Integrin alpha4beta1 - biosynthesis

Lectins - biosynthesis

Hypertension - etiology

Nicotine - pharmacology

Receptor, Angiotensin, Type 1 - biosynthesis

Rats, Inbred SHR

Receptor, Angiotensin, Type 2 - genetics

Angiotensin II - metabolism

Receptor, Angiotensin, Type 2 - biosynthesis

Cells, Cultured

Hypertension, Renal - etiology

Chemokine CCL2 - genetics

Immunophenotyping

Integrin alpha4beta1 - genetics

Nicotine - toxicity

Prehypertension - pathology

Gene Expression Regulation - drug effects

Animals

Norepinephrine - metabolism

Macrophages - drug effects

Cytokines - biosynthesis

Denervation

Details

Title: Subtitle: Nicotine Mediates CD161a+ Renal Macrophage Infiltration and Premature Hypertension in the Spontaneously Hypertensive Rat
Creators: Sailesh C Harwani - From the Department of Internal Medicine (S.C.H., J.R., F.S.S., Z.K.B., M.W.C., F.M.A.), Departments of Molecular Physiology and Biophysics (M.W.C., F.M.A.), and Veterans Affairs Medical Center (F.S.S., Z.K.B., M.W.C.), Iowa City; and Department of Pathology (D.K.M.), Inflammation Program, Department of Internal Medicine (F.S.S.), Center for Immunology and Immune Mediated Diseases (S.C.H., F.S.S., F.M.A.), and Abboud Cardiovascular Research Center (S.C.H., J.R., M.W.C., F.M.A.), University of Iowa Carver College of Medicine, Iowa City. sailesh-harwani@uiowa.edu
Jason Ratcliff - From the Department of Internal Medicine (S.C.H., J.R., F.S.S., Z.K.B., M.W.C., F.M.A.), Departments of Molecular Physiology and Biophysics (M.W.C., F.M.A.), and Veterans Affairs Medical Center (F.S.S., Z.K.B., M.W.C.), Iowa City; and Department of Pathology (D.K.M.), Inflammation Program, Department of Internal Medicine (F.S.S.), Center for Immunology and Immune Mediated Diseases (S.C.H., F.S.S., F.M.A.), and Abboud Cardiovascular Research Center (S.C.H., J.R., M.W.C., F.M.A.), University of Iowa Carver College of Medicine, Iowa City
Fayyaz S Sutterwala - From the Department of Internal Medicine (S.C.H., J.R., F.S.S., Z.K.B., M.W.C., F.M.A.), Departments of Molecular Physiology and Biophysics (M.W.C., F.M.A.), and Veterans Affairs Medical Center (F.S.S., Z.K.B., M.W.C.), Iowa City; and Department of Pathology (D.K.M.), Inflammation Program, Department of Internal Medicine (F.S.S.), Center for Immunology and Immune Mediated Diseases (S.C.H., F.S.S., F.M.A.), and Abboud Cardiovascular Research Center (S.C.H., J.R., M.W.C., F.M.A.), University of Iowa Carver College of Medicine, Iowa City
Zuhair K Ballas - From the Department of Internal Medicine (S.C.H., J.R., F.S.S., Z.K.B., M.W.C., F.M.A.), Departments of Molecular Physiology and Biophysics (M.W.C., F.M.A.), and Veterans Affairs Medical Center (F.S.S., Z.K.B., M.W.C.), Iowa City; and Department of Pathology (D.K.M.), Inflammation Program, Department of Internal Medicine (F.S.S.), Center for Immunology and Immune Mediated Diseases (S.C.H., F.S.S., F.M.A.), and Abboud Cardiovascular Research Center (S.C.H., J.R., M.W.C., F.M.A.), University of Iowa Carver College of Medicine, Iowa City
David K Meyerholz - From the Department of Internal Medicine (S.C.H., J.R., F.S.S., Z.K.B., M.W.C., F.M.A.), Departments of Molecular Physiology and Biophysics (M.W.C., F.M.A.), and Veterans Affairs Medical Center (F.S.S., Z.K.B., M.W.C.), Iowa City; and Department of Pathology (D.K.M.), Inflammation Program, Department of Internal Medicine (F.S.S.), Center for Immunology and Immune Mediated Diseases (S.C.H., F.S.S., F.M.A.), and Abboud Cardiovascular Research Center (S.C.H., J.R., M.W.C., F.M.A.), University of Iowa Carver College of Medicine, Iowa City
Mark W Chapleau - From the Department of Internal Medicine (S.C.H., J.R., F.S.S., Z.K.B., M.W.C., F.M.A.), Departments of Molecular Physiology and Biophysics (M.W.C., F.M.A.), and Veterans Affairs Medical Center (F.S.S., Z.K.B., M.W.C.), Iowa City; and Department of Pathology (D.K.M.), Inflammation Program, Department of Internal Medicine (F.S.S.), Center for Immunology and Immune Mediated Diseases (S.C.H., F.S.S., F.M.A.), and Abboud Cardiovascular Research Center (S.C.H., J.R., M.W.C., F.M.A.), University of Iowa Carver College of Medicine, Iowa City
Francois M Abboud - From the Department of Internal Medicine (S.C.H., J.R., F.S.S., Z.K.B., M.W.C., F.M.A.), Departments of Molecular Physiology and Biophysics (M.W.C., F.M.A.), and Veterans Affairs Medical Center (F.S.S., Z.K.B., M.W.C.), Iowa City; and Department of Pathology (D.K.M.), Inflammation Program, Department of Internal Medicine (F.S.S.), Center for Immunology and Immune Mediated Diseases (S.C.H., F.S.S., F.M.A.), and Abboud Cardiovascular Research Center (S.C.H., J.R., M.W.C., F.M.A.), University of Iowa Carver College of Medicine, Iowa City
Resource Type: Journal article
Publication Details: Circulation research, Vol.119(10), pp.1101-1115
Publisher: United States
DOI: 10.1161/CIRCRESAHA.116.309402
PMID: 27660287
PMCID: PMC5085865
ISSN: 0009-7330
eISSN: 1524-4571
Grant note: T32 AI007517 / NIAID NIH HHS P01 HL014388 / NHLBI NIH HHS K08 HL119588 / NHLBI NIH HHS L30 HL134111 / NHLBI NIH HHS T32 HL007121 / NHLBI NIH HHS
Language: English
Date published: 10/28/2016
Academic Unit: Molecular Physiology and Biophysics; Pathology; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Immunology; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984025422702771

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