Dissolved gases from pressure changes in the lungs elicit an immune response in human peripheral blood

Harrell, A. G.; Thom, S. R.; Shields, C. W.

doi:10.1101/2023.10.18.562856

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bioRxiv · 10.1101/2023.10.18.562856

Dissolved gases from pressure changes in the lungs elicit an immune response in human peripheral blood

Harrell, A. G.·Thom, S. R.·Shields, C. W.

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Abstract

Conventional dogma suggests that decompression sickness (DCS) is caused by nitrogen bubble nucleation in the blood vessels and/or tissues; however, the abundance of bubbles does not correlate with DCS severity. Since immune cells respond to chemical and environmental cues, we hypothesized that the elevated partial pressures of dissolved gases drive aberrant immune cell phenotypes in the alveolar vasculature. To test this hypothesis, we measured immune responses within human lung-on-a-chip devices established with primary alveolar cells and microvascular cells. Devices were pressurized to 1.0 or 3.5 atm and surrounded by normal alveolar air or oxygen-reduced air. Phenotyping of neutrophils, monocytes, and dendritic cells as well as multiplexed ELISA revealed that immune responses occur within 1 hour and that normal alveolar air (i.e., hyperbaric oxygen and nitrogen) confer greater immune activation. This work strongly suggests innate immune cell reactions initiated at elevated partial pressures contribute to the etiology of DCS. Translational Impact StatementOur work reveals that the elevated partial pressures of dissolved gases within the vasculature drives immune cell activation. These findings have broad implications in identifying novel biomarkers for high-risk individuals (e.g., divers, pilots) through screening differential immune markers across patients. Further, this work offers a lens through which novel strategies to mitigate DCS in clinical scenarios may be employed by the delivery of prophylactic drugs that temper immune reactions.

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Harrell, A. G., Thom, S. R., Shields, C. W.. 2023-10-21. Dissolved gases from pressure changes in the lungs elicit an immune response in human peripheral blood. https://doi.org/10.1101/2023.10.18.562856

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