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

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

Stephen R Thom, Ming Yang, Veena M Bhopale, Tatyana N Milovanova, Marina Bogush and Donald G Buerk
Journal of applied physiology (1985), v 114(5), pp 550-558
01 Mar 2013
DOI: https://doi.org/10.1152/japplphysiol.01386.2012
PMID: 23264541
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Animals Annexin A5 - genetics Annexin A5 - metabolism Cell Membrane Permeability - genetics Cell Membrane Permeability - physiology Cell-Derived Microparticles - genetics Cell-Derived Microparticles - metabolism Cholesterol - genetics Cholesterol - metabolism Decompression Sickness - metabolism Inflammation - genetics Inflammation - metabolism Inflammation - physiopathology Mice Mice, Knockout Neutrophil Activation - genetics Neutrophil Activation - physiology Neutrophils - metabolism Nitric Oxide Synthase Type II - antagonists & inhibitors Nitric Oxide Synthase Type II - genetics Nitric Oxide Synthase Type II - metabolism Nitrogen Dioxide - metabolism Osmotic Pressure - physiology Reactive Nitrogen Species - genetics Reactive Nitrogen Species - metabolism Vascular System Injuries - genetics Vascular System Injuries - metabolism
Inert gases diffuse into tissues in proportion to ambient pressure, and when pressure is reduced, gas efflux forms bubbles due to the presence of gas cavitation nuclei that are predicted based on theory but have never been characterized. Decompression stress triggers elevations in number and diameter of circulating annexin V-coated microparticles (MPs) derived from vascular cells. Here we show that ∼10% MPs from wild-type (WT) but not inflammatory nitric oxide synthase-2 (iNOS) knockout (KO) mice increase in size when exposed to elevated air pressure ex vivo. This response is abrogated by a preceding exposure to hydrostatic pressure, demonstrating the presence of a preformed gas phase. These MPs have lower density than most particles, 10-fold enrichment in iNOS, and generate commensurately more reactive nitrogen species (RNS). Surprisingly, RNS only slowly diffuse from within MPs unless particles are subjected to osmotic stress or membrane cholesterol is removed. WT mice treated with iNOS inhibitor and KO mice exhibit less decompression-induced neutrophil activation and vascular leak. Contrary to injecting naïve mice with MPs from wild-type decompressed mice, injecting KO MPs triggers fewer proinflammatory events. We conclude that nitrogen dioxide is a nascent gas nucleation site synthesized in some MPs and is responsible for initiating postdecompression inflammatory injuries.

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36 citations in Web of Science
36 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Physiology
Sport Sciences
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