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

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.

Cardiovascular health effects of oral and pulmonary exposure to multi-walled carbon nanotubes in ApoE-deficient mice

“…Furthermore, it has been shown that repeated i.t. instillations of lipopolysaccharide, once a week for 10 weeks, increased neutrophilic influx in BALF, without alteration to the extent of atherosclerosis in aorta and BCA (Christophersen et al 2016). Thus, we feel it is unlikely that overt pulmonary inflammation is a pre-requisite for these cardiovascular effects in animal models.…”

Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties

“…Inhalation is the golden standard for testing pulmonary toxicity, whereas pulmonary intratracheal instillation allows control of the deposited dose, and is thus suitable for comparison of hazard potential between different particles. We used 0.1% Tween as vehicle [35,59], since all five diesel exhaust particle samples could be dispersed using this vehicle. Furthermore, two different control groups were included, vehicle controls and blank filter extraction controls.…”

Vasomotor function in rat arteries after ex vivo and intragastric exposure to food-grade titanium dioxide and vegetable carbon particles

“…Nevertheless, we speculate that the altered vasomotor response may be due to bioactive components in plasma that interact with the cellular signaling (e.g., NO production or delivery from endothelial cells to smooth muscle cells) or increases the response to vasoactive drugs. Previously, we have shown that plasma from Printex 90 exposed mice caused vasocontraction in aorta rings from naïve mice [ 31 ]. This type of bioactivity has been described in various studies on pulmonary exposure to particulate matter [ 32 ].…”