Harrell Abigail G, Thom Stephen R, Shields C Wyatt
Department of Chemical and Biological Engineering University of Colorado Boulder Boulder Colorado USA.
Department of Emergency Medicine University of Maryland School of Medicine Baltimore Maryland USA.
Bioeng Transl Med. 2024 Apr 16;9(5):e10657. doi: 10.1002/btm2.10657. eCollection 2024 Sep.
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 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.
传统观点认为，减压病（DCS）是由血管和/或组织中的氮气气泡成核引起的；然而，气泡的数量与DCS的严重程度并不相关。由于免疫细胞会对化学和环境信号做出反应，我们推测溶解气体分压的升高会驱动肺泡血管系统中异常的免疫细胞表型。为了验证这一假设，我们在由原代肺泡细胞和微血管细胞构建的人体芯片肺装置中测量了免疫反应。将装置加压至1.0或3.5个大气压，并置于正常肺泡空气或低氧空气中。对中性粒细胞、单核细胞和树突状细胞进行表型分析以及多重ELISA检测发现，免疫反应在1小时内就会发生，并且正常肺泡空气（即高压氧和氮气）会引发更强的免疫激活。这项研究有力地表明，在高压下引发的先天性免疫细胞反应促成了DCS的病因。
