01720nas a2200229   4500000000100000000000100001008004100002653002000043653001100063653002300074653001900097653002000116653004700136100002300183700002000206700002400226245010700250856006300357300001100420520104500431022001401476                                       d10adissolved gases10adiving10ahyperbaric chamber10alung-on-a-chip10aorgan-on-a-chip10aperipheral blood mononuclear cells (PBMCs)1 aAbigail G. Harrell1 aStephen R. Thom1 aC. Wyatt Shields IV00aDissolved gases from pressure changes in the lungs elicit an immune response in human peripheral blood  uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/btm2.10657  ae106573 aConventional 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 h 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.  a2380-6761