Inflammation and vascular effects after repeated intratracheal instillations of carbon black and lipopolysaccharide

Tidsskriftartikel - 2016

Resume

[Open access]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 mug nanosized carbon black (CB) alone or spiked with LPS (0.2 mug/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 naive 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 naive 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 naive wild-type mice, an effect possibly related to increased plasma serotonin

Reference

Christophersen DV, Jacobsen NR, Jensen D, Kermanizadeh A, Sheykhzade M, Loft S, Vogel UB, Wallin EHR, Møller P. Inflammation and vascular effects after repeated intratracheal instillations of carbon black and lipopolysaccharide. PLoS One 2016;11(8):e0160731-.
doi: 10.1371/journal.pone.0160731

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Dansk Center for Nanosikkerhed