Combustion-derived particles inhibit in vitro human lung fibroblast-mediated matrix remodeling

Abstract

BackgroundThe continuously growing human exposure to combustion-derived particles (CDPs) drives in depth investigation of the involved complex toxicological mechanisms of those particles. The current study evaluated the hypothesis that CDPs could affect cell-induced remodeling of the extracellular matrix due to their underlying toxicological mechanisms. The effects of two ultrafine and one fine form of CDPs on human lung fibroblasts (MRC-5 cell line) were investigated, both in 2D cell culture and in 3D collagen type I hydrogels. A multi-parametric analysis was employed.ResultsIn vitro dynamic 3D analysis of collagen matrices showed that matrix displacement fields induced by human lung fibroblasts are disturbed when exposed to carbonaceous particles, resulting in inhibition of matrix remodeling. In depth analysis using general toxicological assays revealed that a plausible explanation comprises a cascade of numerous detrimental effects evoked by the carbon particles, including oxidative stress, mitochondrial damage and energy storage depletion. Also, ultrafine particles revealed stronger toxicological and inhibitory effects compared to their larger counterparts. The inhibitory effects can be almost fully restored when treating the impaired cells with antioxidants like vitamin C.ConclusionsThe unraveled in vitro pathway, by which ultrafine particles alter the fibroblasts’ vital role of matrix remodeling, extends our knowledge about the contribution of these biologically active particles in impaired lung tissue repair mechanisms, and development and exacerbation of chronic lung diseases. The new insights may even pave the way to precautionary actions. The results provide justification for toxicological assessments to include mechanism-linked assays besides the traditional in vitro toxicological screening assays.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0410-x) contains supplementary material, which is available to authorized users.

Urban PM2.5 Induces Cellular Toxicity, Hormone Dysregulation, Oxidative Damage, Inflammation, and Mitochondrial Interference in the HRT8 Trophoblast Cell Line

“…The smaller particles, ultrafine particles (UFPs), have been shown to localize to mitochondria of endothelial cells, where they induce major structural damage (67). Combustion-related particles have also been shown to cause mitochondrial structural damage in lung cells (68,69). Studies on placentas exposed to higher levels of air pollution show placental mitochondrial DNA methylation (70) and decreased placental mitochondrial DNA content (71).…”

Unique emissive behavior of combustion-derived particles under illumination with femtosecond pulsed near-infrared laser light

“…The dual-channel multiphoton microscopy measurements on CDPs and non-CDPs as reference for particulate air-pollutants were performed on NP suspensions in buffered medium and ultrapure water at biologically relevant concentrations of 20 mg ml À1 . 37,38 The light emitted by the particles was detected simultaneously in two separate channels, which are available with most multiphoton microscopes in biomedical research laboratories, as shown in the schematic in Fig. 1a and b.…”

Label-free detection and size estimation of combustion-derived carbonaceous particles in a microfluidic approach

“…We have employed 4 different commercially available CDCPs with different sizes, according to their specifications, to test the abilities of the setup for their selective detection and size determination in aqueous suspensions using biologically relevant concentrations (20 µg/mL). 32,33 Before measuring using DCMPFC setup, the non-incandescence related WL emission of the CDCPs suspensions under illumination with a fs-pulsed NIR laser at 780 nm was double-checked (Figure S2). This emission spectrum shows that the unique WL emitted by CDCPs covers the whole visible spectrum, and hence can be detected in the VISC.…”