PMID- 27660287
OWN - NLM
STAT- MEDLINE
DCOM- 20170512
LR  - 20240326
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 119
IP  - 10
DP  - 2016 Oct 28
TI  - Nicotine Mediates CD161a+ Renal Macrophage Infiltration and Premature 
      Hypertension in the Spontaneously Hypertensive Rat.
PG  - 1101-1115
AB  - RATIONALE: 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. OBJECTIVE: 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. METHODS AND RESULTS: 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 alpha7-nAChR (alpha7-nicotinic acetylcholine 
      receptor) was similar in young SHR and WKY rats. CONCLUSIONS: 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.
CI  - (c) 2016 American Heart Association, Inc.
FAU - Harwani, Sailesh C
AU  - Harwani SC
AD  - 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.
FAU - Ratcliff, Jason
AU  - Ratcliff J
AD  - 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.
FAU - Sutterwala, Fayyaz S
AU  - Sutterwala FS
AD  - 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.
FAU - Ballas, Zuhair K
AU  - Ballas ZK
AD  - 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.
FAU - Meyerholz, David K
AU  - Meyerholz DK
AD  - 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.
FAU - Chapleau, Mark W
AU  - Chapleau MW
AD  - 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.
FAU - Abboud, Francois M
AU  - Abboud FM
AD  - 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.
LA  - eng
GR  - K08 HL119588/HL/NHLBI NIH HHS/United States
GR  - T32 HL007121/HL/NHLBI NIH HHS/United States
GR  - P01 HL014388/HL/NHLBI NIH HHS/United States
GR  - T32 AI007517/AI/NIAID NIH HHS/United States
GR  - L30 HL134111/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20160922
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD68 protein, mouse)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Integrin alpha4beta1)
RN  - 0 (LLT1 protein, mouse)
RN  - 0 (Lectins)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily B)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 11128-99-7 (Angiotensin II)
RN  - 6M3C89ZY6R (Nicotine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Age of Onset
MH  - Angiotensin II/metabolism
MH  - Animals
MH  - Antigens, CD/analysis
MH  - Antigens, Differentiation, Myelomonocytic/analysis
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis/genetics
MH  - Cytokines/biosynthesis/genetics
MH  - Denervation
MH  - Gene Expression Regulation/drug effects
MH  - Hypertension/*etiology/genetics/metabolism/pathology
MH  - Hypertension, Renal/etiology/genetics/metabolism/pathology
MH  - Immunophenotyping
MH  - Integrin alpha4beta1/biosynthesis/genetics
MH  - Kidney/innervation/*pathology
MH  - Lectins/biosynthesis/genetics
MH  - Macrophages/classification/*drug effects/pathology
MH  - Male
MH  - NK Cell Lectin-Like Receptor Subfamily B/analysis
MH  - Nephritis/chemically induced/physiopathology
MH  - Nicotine/*pharmacology/toxicity
MH  - Norepinephrine/metabolism
MH  - Prehypertension/etiology/genetics/pathology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Receptor, Angiotensin, Type 1/biosynthesis/genetics
MH  - Receptor, Angiotensin, Type 2/biosynthesis/genetics
MH  - alpha7 Nicotinic Acetylcholine Receptor/biosynthesis/genetics
PMC - PMC5085865
MID - NIHMS818744
OTO - NOTNLM
OT  - CD161
OT  - CD68
OT  - SHR
OT  - cholinergic
OT  - hypertension
OT  - inflammation
OT  - innate immunity
OT  - integrin
OT  - lectin
OT  - macrophage
OT  - nicotine
OT  - renal
COIS- The authors do not have any disclosures that present a conflict of interest at 
      the time of submission of this manuscript.
EDAT- 2016/10/30 06:00
MHDA- 2017/05/13 06:00
PMCR- 2017/10/28
CRDT- 2016/09/24 06:00
PHST- 2016/06/24 00:00 [received]
PHST- 2016/09/22 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/05/13 06:00 [medline]
PHST- 2016/09/24 06:00 [entrez]
PHST- 2017/10/28 00:00 [pmc-release]
AID - CIRCRESAHA.116.309402 [pii]
AID - 10.1161/CIRCRESAHA.116.309402 [doi]
PST - ppublish
SO  - Circ Res. 2016 Oct 28;119(10):1101-1115. doi: 10.1161/CIRCRESAHA.116.309402. Epub 
      2016 Sep 22.