Microparticle-induced vascular injury in mice following decompression is inhibited by hyperbaric oxygen: Effects on microparticles and interleukin-1

Abstract

Hyperbaric oxygen (HBO2) became a mainstay for treating decompression sickness (DCS) because bubbles are associated with the disorder. Inflammatory processes including production of circulating microparticles (MPs) have now been shown to occur with DCS, leading to questions regarding pathophysiology and the role for HBO2. We investigated effects of HBO2 on mice exposed to 790 kPa air pressure for 2 h, which triggers elevations of MPs ladened with interleukin (IL)-1 that cause diffuse vascular injuries. Exposure to 283 kPa O2 (HBO2) inhibited MP elevations at 2 h postdecompression by 50% when applied either prophylactically or as treatment after decompression, and the MP number remained suppressed for 13 h in the prophylactic group. Particle content of IL-1 at 2 h postdecompression was 139.3 16.2 [means SE; n 11, P 0.05) pg/million MPs vs. 8.2 1.0 (n 15) in control mice, whereas it was 31.5 6.1 (n 6, not significant vs. control (NS)] in mice exposed to HBO2 prophylactically, and 16.6 6.3 (n 7, NS) when HBO2 was administered postdecompression. IL-1 content in MPs was similar in HBO2-exposed mice at 13 h postdecompression. HBO2 also inhibited decompression-associated neutrophil activation and diffuse vascular leak. Immunoprecipi-tation studies demonstrated that HBO2 inhibits high-pressure-mediated neutrophil nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome oligomerization. Furthermore, MPs isolated from decompressed mice cause vascular injuries when injected into naïve mice, but if decompressed mice were exposed to HBO2 before MP harvest, vascular injuries were inhibited. We conclude that HBO2 impedes high-pressure/decompression-mediated inflammatory events by inhibiting inflammasome formation and IL-1 production. NEW & NOTEWORTHY High pressure/decompression causes vascular damage because it stimulates production of microparticles that contain high concentrations of interleukin-1, and hyperbaric oxygen can prevent injuries.