PMID- 23264541
OWN - NLM
STAT- MEDLINE
DCOM- 20140113
LR  - 20130304
IS  - 1522-1601 (Electronic)
IS  - 0161-7567 (Linking)
VI  - 114
IP  - 5
DP  - 2013 Mar 1
TI  - Intramicroparticle nitrogen dioxide is a bubble nucleation site leading to 
      decompression-induced neutrophil activation and vascular injury.
PG  - 550-8
LID - 10.1152/japplphysiol.01386.2012 [doi]
AB  - 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  approximately 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 naive 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.
FAU - Thom, Stephen R
AU  - Thom SR
AD  - Institute for Environmental Medicine, Univ. of Pennsylvania, Philadelphia, PA 
      19104-6068, USA. sthom@mail.med.upenn.edu
FAU - Yang, Ming
AU  - Yang M
FAU - Bhopale, Veena M
AU  - Bhopale VM
FAU - Milovanova, Tatyana N
AU  - Milovanova TN
FAU - Bogush, Marina
AU  - Bogush M
FAU - Buerk, Donald G
AU  - Buerk DG
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20121220
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Annexin A5)
RN  - 0 (Reactive Nitrogen Species)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - S7G510RUBH (Nitrogen Dioxide)
SB  - IM
MH  - Animals
MH  - Annexin A5/genetics/metabolism
MH  - Cell Membrane Permeability/genetics/physiology
MH  - Cell-Derived Microparticles/genetics/*metabolism
MH  - Cholesterol/genetics/metabolism
MH  - Decompression Sickness/*metabolism
MH  - Inflammation/genetics/metabolism/physiopathology
MH  - Mice
MH  - Mice, Knockout
MH  - Neutrophil Activation/genetics/*physiology
MH  - Neutrophils/metabolism
MH  - Nitric Oxide Synthase Type II/antagonists & inhibitors/genetics/metabolism
MH  - Nitrogen Dioxide/*metabolism
MH  - Osmotic Pressure/physiology
MH  - Reactive Nitrogen Species/genetics/metabolism
MH  - Vascular System Injuries/genetics/*metabolism
EDAT- 2012/12/25 06:00
MHDA- 2014/01/15 06:00
CRDT- 2012/12/25 06:00
PHST- 2012/12/25 06:00 [entrez]
PHST- 2012/12/25 06:00 [pubmed]
PHST- 2014/01/15 06:00 [medline]
AID - japplphysiol.01386.2012 [pii]
AID - 10.1152/japplphysiol.01386.2012 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2013 Mar 1;114(5):550-8. doi: 
      10.1152/japplphysiol.01386.2012. Epub 2012 Dec 20.