Air-Liquid Interface: Relevant In Vitro Models for Investigating Air Pollutant-Induced Pulmonary Toxicity

Abstract

Air pollution leads to inhalation of several pulmonary stimulants that includes particulate matter, and gaseous substances contributing significantly to the development of chronic lung diseases. However, the pathophysiological mechanism of air pollutant mediated pulmonary toxicity remains unclear. This is primarily due to the lack of efficient test systems, mimicing human inhalation exposure scenarios to air pollutants. The majority of the pulmonary in vitro studies have been conducted using cell lines in submerged cell culture conditions and thereby overlooking the pulmonary physiology. Moreover, submerged cell culture systems lack the possibility to measure effective dose measurements. Particle properties, such as size, surface charge, solubility, transformation, or agglomeration state and chemical properties are altered in solution and are dependent on the composition of cell culture medium. Physiologically relevant in vivo-like in vitro models cultured at air-liquid interface (ALI) is therefore becoming a realistic and efficient tool for lung toxicity testing and cell-cell interaction studies following exposure to aerosolized or gaseous form of air pollutants. Primary bronchial epithelial cells cultured at ALI leads to differentiate into respiratory epithelium consisting of ciliated cells, goblet cells, club cells and basal cells. ALI system is also considered as a feasible approach to implement the "3R principle"-replacement, reduction, and refinement of animal usage in lung toxicity studies. This review discusses the current understanding of relevance, benefits and limitations of the ALI models in comparison to the existing in vitro and in vivo exposure system for testing air pollutants mediated pulmonary toxicity.

Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract

“…Secretory cell differentiation of lung epithelium can be modeled in vitro by culturing cells at an air-liquid interface (ALI) 70,71 . Under appropriate conditions, primary respiratory cells growing at an ALI will undergo mucociliary differentiation into a stratified epithelium consisting of ciliated cells, goblet cells, and club cells 72 .…”

Microcystin-LR Does Not Alter Cell Survival and Intracellular Signaling in Human Bronchial Epithelial Cells

“…MC-LR also decreased the expression of tight junction proteins in murine Sertoli cells [69]. Therefore, further studies, preferably with physiologically more relevant human in vitro models, such as filter-insert cultures or 3D air-liquid interface (ALI) cultures of bronchial epithelial cells [70] should focus on tight junctions and barrier function modulation in response to cyanotoxins, especially in combination with relevant exposure estimates and scenarios.…”

“…Further, more detailed studies are needed to better characterize concentrations of toxic cyanobacteria and cyanotoxins in aerosols and to more accurately assess and quantify the inhalation exposures and concentrations/doses of cyanotoxins relevant for the airway epithelium. Advanced human in vitro airway epithelium models, such as ALI cultures of immortalized human bronchial epithelial cells, possibly in co-cultures with different cell types [70] shall be considered because they allow for toxicologically more relevant toxin administration in contrast to fully submerged cell cultures. In combination with better estimates of environmental exposures, such an approach would contribute to improved assessment of human health risks associated with inhalation of cyanotoxins.…”

Is the particle deposition in a cell exposure facility comparable to the lungs? A computer model approach

“…Particle exposure of cell culture tissue at the air-liquid interface (ALI) is frequently used to assess toxicological endpoints and can be considered as an indicator for adverse health effects (Upadhyay and Palmberg 2018). The benefits of cell exposures at the ALI include reproducibility, physiological relevance in respiratory research and short-term or acute to mid-term exposures.…”