Comprehensive analysis of resilience of human airway epithelial barrier against short-term PM2.5 inorganic dust exposure using in vitro microfluidic chip and ex vivo human airway models

Background and Objective: The updated World Health Organization (WHO) air quality guideline recommends an annual mean concentration of fine particulate matter (PM2.5) not exceeding 5 or 15 mu g/m(3) in the short-term (24 h) for no more than 3-4 days annually. However, more than 90% of the global population is currently exposed to daily concentrations surpassing these limits, especially during extreme weather conditions and due to transboundary dust transport influenced by climate change. Herein, the effect of respirable

Methods: Silica particles at an average size of 1 mu m, referred to as

Results: In the AEB-on-a-chip platform, short-term exposure to 800 mu g/mL PM2.5 disrupted AEB integrity via increasing barrier permeability, decreasing cell adhesion-barrier markers such as ZO-1, Vinculin, ACE2, and CD31, impaired cell viability and increased the expression levels of proinflammatory markers; IFNs, IL-6, IL-1s, TNF-alpha, CD68, CD80, and Inos, mostly under dynamic conditions. Besides, decreased tissue viability, impaired tissue integrity via decreasing of Vinculin, ACE2, beta-catenin, and E-cadherin, and also proinflammatory response with elevated CD68, IL-1 alpha, IL-6, IFN-gamma, Inos, and CD80 markers, were observed after PM2.5 exposure in ex vivo tissue.

Conclusion: The duration and concentration of PM2.5 that can be exposed during extreme weather conditions and natural events aligns with our exposure model (0-800 mu g/mL 72 h). At this level of exposure, the resilience of the epithelial barrier is demonstrated by both AEB-on-a-chip platform emulating dynamic forces in the body and ex vivo bronchial biopsy slices. Lung-on-a-chip models will serve as reliable exposure models in this context.