3.2 Modeling and characterizing fire-related SI-ALI on the LOC
The combustion control system and non-metallic materials, including
polyimide foam, rubber, sound insulation pads, acrylic paint, floor
adhesive, nitrile rubber, and modified ethylene resin, are illustrated
in Figures 2B-a and 2B-c. Combustion byproducts were monitored using a
portable Fourier Transform Infrared Spectrometer (FTIR) (Figure 2B-b).
To evaluate combustion stability, emissions of gases, including nitrous
oxide (N₂O), carbon monoxide (CO), styrene (C₈H₈), and hydrogen cyanide
(HCN), were quantified. The results showed consistent trends in the
concentration changes of these gases across different batches of
material during combustion (Supplementary Figure 2C), with detailed
compositions provided in Supplementary Text 1.
To replicate the SI-ALI process observed in vivo (Figures 1A and 3F),
the collected smoke was introduced into the lower compartments of the
lung chip using a syringe to simulate alveolar smoke exposure (Figure
2C). Oxidative stress and apoptosis assays demonstrated increased ROS
production (Figure 3C) and elevated cell apoptosis (Figure 3A) following
smoke exposure. Transmission electron microscopy (TEM) revealed
significant damage to the mitochondria and endoplasmic reticulum (Figure
3E). Leakage assays detected the rapid translocation of macromolecular
substances (FITC-dextran, 40 kDa) from the vascular to the alveolar
channel under smoke exposure (Figure 3B), indicating a compromised
alveolar-capillary barrier. Additionally, a marked increase in the
adhesion of activated THP-1 cells to the barrier was observed in the
smoke-exposed group compared to the control group (Figure 3D).
Inflammation- and apoptosis-related genes, including IL-6, TNF-α, and
caspase-3, were upregulated in both epithelial and endothelial cells
(Figure 4A-b, c, e), while IL-1β and NF-κB were predominantly
upregulated in epithelial cells alone (Figure 4A-a, f). Notably, IL-10
expression remained unchanged (Figure 4A-d). ELISA results further
confirmed that smoke exposure stimulates the release of TNF-α, IL-6, and
IL-1β, independent of THP-1 cell presence (Figure 4B). These findings
underscore the detrimental impact of smoke on the alveolar-capillary
barrier, including the induction of oxidative stress, cellular
apoptosis, mitochondrial damage, and the initiation of an inflammatory
cascade accompanied by enhanced inflammatory cell adhesion.