Microparticles, Platelet-Neutrophil Aggregation, and Decompression Sickness
Abstract
Decompression sickness (DCS) is a systemic pathological process that occurs when tissues become super-saturated with one or more gases. The central place of bubbles in the etiology of DCS is widely accepted, but the responses that mediate tissue injury remain unclear. This proposal is centered on the hypothesis that circulating microparticles (MPs, 0.1- 1 micrometer diameter vesicles produced by all vascular cells) are the proximal cause for organ injuries following decompression stress because they initiate an inflammatory response. It has been shown in both laboratory animals and humans that circulating MPs are elevated in association with exposures to high gas pressures. Recent studies have found strong positive correlations between circulating MPs and ultrasound-detected bubbles under some dive conditions, suggesting a mechanistic association. Divers with DCS exhibit differences from asymptomatic divers in terms of circulating MPs and neutrophil activation. This proposal is focused on MPs and other decompression-related events in a murine model, where MPs have been shown to be the etiological agent causing tissue damage post-decompression. Interventions that diminish circulating MPs also abrogate decompression-induced tissue injury, and many of the same interventions reduce circulating MPs in human divers. MPs purified from decompressed mice can be injected into na~ve mice and induce exactly the same pathological responses as does decompression. The ultimate goal of this project is to elucidate the pathophysiology of DCS.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 30, 2016
- Source ID
- N000141612868
Entities
People
- Stephen R. Thom
Organizations
- Office of Naval Research
- United States Navy
- University of Maryland