Microparticles initiate decompression-induced neutrophil activation and subsequent vascular injuries

Abstract

Progressive elevations in circulating annexin V-coated microparticles (MPs) derived from leukocytes, erythrocytes, platelets, and endothelial cells are found in mice subjected to increasing decompression stresses. Individual MPs exhibit surface markers from multiple cells. MPs expressing platelet surface markers, in particular, interact with circulating neutrophils, causing them to degranulate and leading to further MP production. MPs can be lysed by incubation with polyethylene glycol (PEG) telomere B surfactant, and the number of circulating MPs is reduced by infusion of mice with PEG or antibody to annexin V. Myeloperoxidase deposition and neutrophil sequestration in tissues occur in response to decompression, and the pattern differs among brain, omentum, psoas, and leg skeletal muscle. Both MP abatement strategies reduce decompression-induced intravascular neutrophil activation, neutrophil sequestration, and tissue injury documented as elevations of vascular permeability and activated caspase-3. We conclude that MPs generated by decompression stresses precipitate neutrophil activation and vascular damage.

Intramicroparticle nitrogen dioxide is a bubble nucleation site leading to decompression-induced neutrophil activation and vascular injury

“…A colony of iNOS KO mice, initially purchased from Jackson Laboratories, was maintained in the University vivarium. Mice were left to breathe room air (control) or subjected to 790 kPa (100 pounds per square inch) air pressure for 2 h following our published procedures (32,41).…”

“…Endothelial leakage was evaluated 1 h after injection. Mice were anesthetized, exsanguinated, injected with lysine fixable Rhodamine-dextran (2 ϫ 10 6 Da) and then with colloidal silica following published methods (32). Endotheliumenriched fractions were obtained for analysis from brain, leg skeletal muscle, psoas, and omentum.…”

“…Flow cytometry was performed with a 10-color FACSCanto (Becton Dickinson, San Jose, CA) using standard acquisition software. Analysis of neutrophils and MPs was performed as previously described (32,41).…”

“…Recent studies have shown that some annexin V-positive particles enlarge beyond 1 m in diameter during decompression (31,32,41). When injected into naïve mice, these large particles will recapitulate the pathophysiological vascular changes observed with provocative decompression (41).…”

“…MPs were shown to be responsible for inflammatory vascular injuries in a murine DCS model (32). MPs are defined as membrane lipid bilayer-enclosed vesicles with a diameter of 0.1-1.0 m. MPs are present in peripheral blood of healthy individuals, increase with traumatic and inflammatory disorders, and may serve as intercellular messengers because they can contain cytokines or other signaling proteins, mRNA, and microRNA (19).…”