Endothelial cells as biosensors to assess the vascular inflammatory potential of serum following nanomaterial exposure.
Aragon-M; Dunlap-M; Roberts-JR; Erdely-A; Campen-M
Toxicologist 2014 Mar; 138(1):523
Assessing mechanisms underlying the adverse vascular health effects of systemic inflammation induced by inhaled toxins presents a substantial research challenge. We have developed an ex vivo model that allows for a realistic exposure method to better elucidate the mechanisms involved in a living system. This approach applies serum from exposed animals to cultured primary endothelial cells, as this is the component in direct contact with the vascular endothelium. Here, we apply this assay paradigm to assess the impact of pulmonary exposures to multi-walled carbon nanotubes (MWCNT) or graphene. Mice were exposed to varying doses (4, 10 or 40 mg) of MWCNT, various types of graphene, or carbon black via pharyngeal aspiration, and serum was collected at 4 and 24 h post-exposure. Serum collected from 19 d inhalation exposures to 0.5 or 5.0 mg/m3 MWCNT was also assayed for endothelial activation. Serum from exposed mice induced an up-regulation of endothelial cell surface VCAM and ICAM expression, along with elevations in mRNA at the 4 h time point. Multiple sizes of graphene were tested; the smallest sizes (<2 mm x <2 mm x 1-2 nm and 5 mm x 5 mm x 7 nm) induced up-regulation of surface VCAM, but were overall less potent than carbon black, used as a control particle. Furthermore, we assessed nitric oxide (NO) generation by endothelial cells using electron paramagnetic resonance (EPR) methods, and found that NO was decreased via treatment with serum from MWCNT-exposed mice following stimulation with 2 mM ATP. Microarray analysis of endothelial cell response to serum from the inhalation and instillation exposures revealed a common set of response elements. In conclusion, pulmonary exposure to carbon-based nanomaterials alters circulating factors which promote endothelial cell activation and decreased NO bioavailability.
Toxicology; Exposure-levels; Nanotechnology; Toxins; Chemical-composition; Chemical-properties; Particulates; Cell-biology; Cell-function; Cellular-function; Animals; Laboratory-animals; Lung; Lung-function; Lung-tissue; Respiratory-system-disorders; Pulmonary-function; Pulmonary-function-tests; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Mortality-rates; Morbidity-rates
1333-86-4; 10102-43-9; 7631-86-9
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona