A novel, easy-to-use cell exposure system (ALICE) for controlled pharmaco-toxicological studies with liquids at the air-liquid interface

Lenz, AG; Lentner, Bernd; Dittrich, V; Brandenberger, Christina; Rothen-Rutishauser, B; Schulz, Herbert; Ferron, GA; Karg, E; Schmid, Otmar

doi:10.1055/s-0029-1247932

Cited by 2 publications

(2 citation statements)

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“…In addition, MAC and AEC were observed under in vitro conditions using rat cell lines, which do not accurately mimic the conditions in a living organism. There are also other in vitro approaches using an air-liquid interface (with nebulization of the nanoparticles) which might simulate a more realistic particle exposure scenario 42 . Secretion of MCP-1 protein, but not of CINC-1 and TNF-α protein was in the detection range of the ELISAs which represents another limitation of the used experimental approaches.…”

Section: Ros-mediated Decrease In Viability Of Macrophages Only Margmentioning

confidence: 99%

Inflammatory Response of Lung Macrophages and Epithelial Cells after Exposure to Redox Active Nanoparticles: Effect of Solubility and Antioxidant Treatment

Urner

Schlicker

Z’graggen

et al. 2014

Environ. Sci. Technol.

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The effects of an exposure to three mass-produced metal oxide nanoparticles-similar in size and specific surface area but different in redox activity and solubility-were studied in rat alveolar macrophages (MAC) and epithelial cells (AEC). We hypothesized that the cell response depends on the particle redox activity and solubility determining the amount of reactive oxygen species formation (ROS) and subsequent inflammatory response. MAC and AEC were exposed to different amounts of Mn3O4 (soluble, redox-active), CeO2 (insoluble, redox-active), and TiO2 (insoluble, redox-inert) up to 24 h. Viability and inflammatory response were monitored with and without coincubation of a free-radical scavenger (trolox). In MAC elevated ROS levels, decreased metabolic activity and attenuated inflammatory mediator secretion were observed in response to Mn3O4. Addition of trolox partially resolved these changes. In AEC, decreased metabolic activity and an attenuated inflammatory mediator secretion were found in response to CeO2 exposure without increased production of ROS, thus not sensitive to trolox administration. Interestingly, highly redox-active soluble particles did not provoke an inflammatory response. The data reveal that target and effector cells of the lung react in different ways to particle exposure making a prediction of the response depending on redox activity and intracellular solubility difficult. ABSTRACTThe effects of an exposure to three mass-produced metal oxide nanoparticles -similar in size and specific surface area, but different in redox activity and solubility -were studied in rat alveolar macrophages (MAC) and epithelial cells (AEC). We hypothesized that the cell response depends on the particle redox activity and solubility determining the amount of reactive oxygen species formation (ROS) and subsequent inflammatory response. MAC and AEC were exposed to different amounts of Mn 3 O 4 (soluble, redox-active), CeO 2 (insoluble, redox-active), and TiO 2 (insoluble, redox-inert) up to 24 hours. Viability and inflammatory response were monitored with and without co-incubation of a free-radical scavenger (trolox).In MAC elevated ROS levels, decreased metabolic activity and attenuated inflammatory mediator secretion were observed in response to Mn 3 O 4 . Addition of trolox partially resolved these changes. In AEC, decreased metabolic activity and an attenuated inflammatory mediator secretion were found in response to CeO 2 exposure without increased production of ROS, thus not sensitive to trolox administration. Interestingly, highly redox-active soluble particles did not provoke an inflammatory response. The data reveal that target and effector cells of the lung react in different ways to particle exposure making a prediction of the response depending from redox activity and intracellular solubility difficult.

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Section: Ros-mediated Decrease In Viability Of Macrophages Only Margmentioning

confidence: 99%

Inflammatory Response of Lung Macrophages and Epithelial Cells after Exposure to Redox Active Nanoparticles: Effect of Solubility and Antioxidant Treatment

Urner

Schlicker

Z’graggen

et al. 2014

Environ. Sci. Technol.

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“…33−37 However, there are limitations and challenges to each method. 26,29,37 Thermophoresis applies a temperature gradient where particles move from the hot side to the cold side. Particles larger than the mean free path, 66 nm, will experience a temperature gradient within themselves, and therefore, the total force experienced by the particles will change based on the particle size and the thermal conductivity of the material.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Aerosol Exposure to Nanomaterials: From Laboratory to Environmental Field Toxicity Testing

Tilly

Nelson

Chakravarthy

et al. 2019

Chem. Res. Toxicol.

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Exposure to nanomaterials (NMs) is inevitable, requiring robust toxicological assessment to understand potential environmental and human health effects. NMs are favored in many applications because of their small size; however, this allows them to easily aerosolize and, subsequently, expose humans via inhalation. Toxicological assessment of NMs by conventional methods in submerged cell culture is not a relevant way to assess inhalation toxicity of NMs because of particle interference with bioassays and changes in particokinetics when dispersed in medium. Therefore, an in vitro aerosol exposure chamber (AEC) was custom designed and used for direct deposition of NMs from aerosols in the environment to the air−liquid interface of lung cells. Human epithelial lung cell line, A549, was used to assess the toxicity of copper, nickel, and zinc oxide nanopowders aerosolized by acoustic agitation in laboratory study. Post optimization, the AEC was used in the field to expose the A549 cells to NM aerosols generated from firing a hand gun and rifle. Toxicity was assessed using nondestructive assays for cell viability and inflammatory response, comparing the biologic effect to the delivered mass dose measured by inductively coupled plasmamass spectrometry. The nanopowder exposure to submerged and ALI cells resulted in dose-dependent toxicity. In the field, weapon exhaust from the M4 reduced cell viability greater than the M9, while the M9 stimulated inflammatory cytokine release of IL-8. This study highlights the use of a portable chamber with the capability to assess toxicity of NM aerosols exposed to air− liquid interface in vitro lung cell culture.

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A novel, easy-to-use cell exposure system (ALICE) for controlled pharmaco-toxicological studies with liquids at the air-liquid interface

Cited by 2 publications

References 0 publications

Inflammatory Response of Lung Macrophages and Epithelial Cells after Exposure to Redox Active Nanoparticles: Effect of Solubility and Antioxidant Treatment

Inflammatory Response of Lung Macrophages and Epithelial Cells after Exposure to Redox Active Nanoparticles: Effect of Solubility and Antioxidant Treatment

In Vitro Aerosol Exposure to Nanomaterials: From Laboratory to Environmental Field Toxicity Testing

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