Inflammation and Vascular Effects after Repeated Intratracheal Instillations of Carbon Black and Lipopolysaccharide

Daniel Vest Christophersen, Nicklas Raun Jacobsen, Ditte Marie Jensen, Ali Kermanizadeh, Majid Sheykhzade, Steffen Loft, Ulla Vogel, Håkan Wallin, Peter Møller

Research output: Contribution to journalArticle

Abstract

Inflammation and oxidative stress are considered the main drivers of vasomotor dysfunction and progression of atherosclerosis after inhalation of particulate matter. In addition, new studies have shown that particle exposure can induce the level of bioactive mediators in serum, driving vascular- and systemic toxicity. We aimed to investigate if pulmonary inflammation would accelerate nanoparticle-induced atherosclerotic plaque progression in Apolipoprotein E knockout (ApoE-/-) mice. ApoE -/- mice were exposed to vehicle, 8.53 or 25.6 μg nanosized carbon black (CB) alone or spiked with LPS (0.2 μg/mouse/exposure; once a week for 10 weeks). Inflammation was determined by counting cells in bronchoalveolar lavage fluid. Serum Amyloid A3 (Saa3) expression and glutathione status were determined in lung tissue. Plaque progression was assessed in the aorta and the brachiocephalic artery. The effect of vasoactive mediators in plasma of exposed ApoE-/- mice was assessed in aorta rings isolated from naïve C57BL/6 mice. Pulmonary exposure to CB and/or LPS resulted in pulmonary inflammation with a robust influx of neutrophils. The CB exposure did not promote plaque progression in aorta or BCA. Incubation with 0.5% plasma extracted from CB-exposed ApoE-/- mice caused vasoconstriction in aorta rings isolated from naïve mice; this effect was abolished by the treatment with the serotonin receptor antagonist Ketanserin. In conclusion, repeated pulmonary exposure to nanosized CB and LPS caused lung inflammation without progression of atherosclerosis in ApoE-/- mice. Nevertheless, plasma extracted from mice exposed to nanosized CB induced vasoconstriction in aortas of naïve wild-type mice, an effect possibly related to increased plasma serotonin.

Original languageEnglish
Article numbere0160731
JournalPLoS ONE
Volume11
Issue number8
DOIs
Publication statusPublished - 29 Aug 2016

Keywords

  • Animals
  • Aorta/pathology
  • Apolipoproteins E/genetics
  • Atherosclerosis/pathology
  • Brachiocephalic Trunk
  • Bronchoalveolar Lavage
  • Bronchoalveolar Lavage Fluid
  • Female
  • Glutathione Disulfide/metabolism
  • Intubation, Intratracheal
  • Lipopolysaccharides/administration & dosage
  • Lung/drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Particulate Matter/toxicity
  • Plaque, Atherosclerotic/pathology
  • Pneumonia/chemically induced

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    Christophersen, D. V., Jacobsen, N. R., Jensen, D. M., Kermanizadeh, A., Sheykhzade, M., Loft, S., Vogel, U., Wallin, H., & Møller, P. (2016). Inflammation and Vascular Effects after Repeated Intratracheal Instillations of Carbon Black and Lipopolysaccharide. PLoS ONE, 11(8), [e0160731]. https://doi.org/10.1371/journal.pone.0160731