An in vitro coculture system for the detection of sensitization following aerosol exposure

Abstract

represents the most prevalent occupational disease of the lungs in developed countries and occupational exposure to dusts, gases, fumes, vapors, and chemicals is responsible for 16% of asthma in adults (Torén and Blanc, 2009). Around a hundred chemicals were described to act as respiratory sensitizers (Bloemen et al., 2009), among which different chemical classes such as acid anhydrides, diisocyanates, and chloroplatinate salts were identified.Protein allergens (or high molecular weight; HMW compounds), which are also a potential cause of occupational asthma, are the primary cause for the development of respiratory allergy in the general population. Certain proteins from environmental sources such as pollen, animal dander and house dust mites (HDM) are common causes of asthma. Depending on the geographical location, 50 to 85% of people with asthma are allergic to certain HDM proteins (Gregory and Lloyd, 2011).An early identification of compounds with the potential to act as respiratory sensitizers is still difficult. This is due to an incomplete understanding of the systemic mechanisms involved in the development of respiratory sensitization and to the absence of fit-for-purpose, validated, or even widely accepted in vivo models or in vitro assays to identify respiratory sensitizers. Currently,

Advanced Respiratory Models for Hazard Assessment of Nanomaterials—Performance of Mono-, Co- and Tricultures

“…Closer to the scenario in vivo is the exposure of cells at the air–liquid interface (ALI), where cells cultivated on porous membranes are in direct contact with the air on one side and cell culture media on the other [ 9 , 25 , 26 , 27 , 28 ]. The aim of this work was to test for potential change in sensitivity for toxic insults when going from mono- to tricultures, and to test the robustness of and optimize an advanced 3D lung model in combination with an aerosol exposure system (VITROCELL ® cloud-chamber), to feature the air–blood barrier in the alveoli of the lower respiratory tract by performing and an interlaboratory trial across two laboratories.…”

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

“…The last years increasing attention has been paid to: a) develop in vitro systems for high throughput screening for studying NPs [41] b) identify adverse outcome pathways (AOP) and their critical molecular initiating events (MIEs) for NPs [42] c) develop relevant 3D co-cultures better mimicking the in vivo situations [43][44][45][46][47]. In several studies THP-1 monocytes or PMA-differentiated THP-1 monocytes (THP-1 macrophages), have been included in the apical or basolateral compartment [43,48].…”

Perspective on Multimodal Imaging Techniques Coupling Mass Spectrometry and Vibrational Spectroscopy: Picturing the Best of Both Worlds

“… 36 Cell–cell interaction analysis is also crucial when designing organoid models such as the coculture model of the alveolar barrier, which includes several types of cells: alveolar type II epithelial cells, endothelial cells, macrophages, and dendritic cells. 37 This model was used to discriminate chemical respiratory sensitizers from irritants. Multimodal imaging could be used to monitor oxidative stress, a common consequence of exposure to some toxicants, including nanoparticles, in cells and organoid models through DNA damage and changes in lipid peroxidation.…”

“…For example, molecular images collected with SIMS MSI established the silver nanoparticle uptake of Caco-2/TC7 and HT29-MTX cells by analyzing intracellular localization in relation to particle size . Cell–cell interaction analysis is also crucial when designing organoid models such as the coculture model of the alveolar barrier, which includes several types of cells: alveolar type II epithelial cells, endothelial cells, macrophages, and dendritic cells . This model was used to discriminate chemical respiratory sensitizers from irritants.…”