Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures

Kelly S. Schweitzer, Steven X. Chen, Sarah Law, Mary Van Demark, Christophe Poirier, Matthew J. Justice, Walter C. Hubbard, Elena S. Kim, Xianyin Lai, Mu Wang, William D. Kranz, Clinton J. Carroll, Bruce D. Ray, Robert Bittman, John Goodpaster, Irina Petrache

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1–20 mM nicotine) or to nicotinefree CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10–20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

Original languageEnglish (US)
Pages (from-to)L175-L187
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume309
Issue number2
DOIs
StatePublished - Jul 15 2015

Fingerprint

Nicotine
Tobacco Products
Smoke
Lung
Endothelial Cells
Oxidative Stress
Myosin-Light-Chain Phosphatase
Cell Proliferation
Acrolein
rho-Associated Kinases
Propylene Glycol
Myosin Light Chains
Ceramides
Lung Injury
p38 Mitogen-Activated Protein Kinases
Microvessels
Electric Impedance
Glycerol
Gas Chromatography-Mass Spectrometry
Cultured Cells

Keywords

  • Cell proliferation
  • Inflammation
  • Permeability
  • Sphingosine-1-phosphate
  • Tobacco

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures. / Schweitzer, Kelly S.; Chen, Steven X.; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J.; Hubbard, Walter C.; Kim, Elena S.; Lai, Xianyin; Wang, Mu; Kranz, William D.; Carroll, Clinton J.; Ray, Bruce D.; Bittman, Robert; Goodpaster, John; Petrache, Irina.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 309, No. 2, 15.07.2015, p. L175-L187.

Research output: Contribution to journalArticle

Schweitzer, KS, Chen, SX, Law, S, Van Demark, M, Poirier, C, Justice, MJ, Hubbard, WC, Kim, ES, Lai, X, Wang, M, Kranz, WD, Carroll, CJ, Ray, BD, Bittman, R, Goodpaster, J & Petrache, I 2015, 'Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 309, no. 2, pp. L175-L187. https://doi.org/10.1152/ajplung.00411.2014
Schweitzer, Kelly S. ; Chen, Steven X. ; Law, Sarah ; Van Demark, Mary ; Poirier, Christophe ; Justice, Matthew J. ; Hubbard, Walter C. ; Kim, Elena S. ; Lai, Xianyin ; Wang, Mu ; Kranz, William D. ; Carroll, Clinton J. ; Ray, Bruce D. ; Bittman, Robert ; Goodpaster, John ; Petrache, Irina. / Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2015 ; Vol. 309, No. 2. pp. L175-L187.
@article{735fdbc5301041a890db1815caaa14df,
title = "Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures",
abstract = "The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1–20 mM nicotine) or to nicotinefree CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10–20{\%}) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.",
keywords = "Cell proliferation, Inflammation, Permeability, Sphingosine-1-phosphate, Tobacco",
author = "Schweitzer, {Kelly S.} and Chen, {Steven X.} and Sarah Law and {Van Demark}, Mary and Christophe Poirier and Justice, {Matthew J.} and Hubbard, {Walter C.} and Kim, {Elena S.} and Xianyin Lai and Mu Wang and Kranz, {William D.} and Carroll, {Clinton J.} and Ray, {Bruce D.} and Robert Bittman and John Goodpaster and Irina Petrache",
year = "2015",
month = "7",
day = "15",
doi = "10.1152/ajplung.00411.2014",
language = "English (US)",
volume = "309",
pages = "L175--L187",
journal = "American Journal of Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures

AU - Schweitzer, Kelly S.

AU - Chen, Steven X.

AU - Law, Sarah

AU - Van Demark, Mary

AU - Poirier, Christophe

AU - Justice, Matthew J.

AU - Hubbard, Walter C.

AU - Kim, Elena S.

AU - Lai, Xianyin

AU - Wang, Mu

AU - Kranz, William D.

AU - Carroll, Clinton J.

AU - Ray, Bruce D.

AU - Bittman, Robert

AU - Goodpaster, John

AU - Petrache, Irina

PY - 2015/7/15

Y1 - 2015/7/15

N2 - The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1–20 mM nicotine) or to nicotinefree CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10–20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

AB - The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1–20 mM nicotine) or to nicotinefree CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10–20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

KW - Cell proliferation

KW - Inflammation

KW - Permeability

KW - Sphingosine-1-phosphate

KW - Tobacco

UR - http://www.scopus.com/inward/record.url?scp=84937404195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937404195&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00411.2014

DO - 10.1152/ajplung.00411.2014

M3 - Article

C2 - 25979079

AN - SCOPUS:84937404195

VL - 309

SP - L175-L187

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1040-0605

IS - 2

ER -