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Title: Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

Abstract

We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries.more » - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.« less

Authors:
;  [1];  [2];  [3]; ;  [1];  [1]
  1. Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)
  2. Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)
  3. Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)
Publication Date:
OSTI Identifier:
22285520
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 273; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BRAIN; CARBON MONOXIDE; INFLAMMATION; INHALATION; INJURIES; MICE; NEUTROPHILS; POLYETHYLENE GLYCOLS; SURFACTANTS

Citation Formats

Xu, Jiajun, Yang, Ming, Kosterin, Paul, Salzberg, Brian M., Milovanova, Tatyana N., Bhopale, Veena M., and Thom, Stephen R., E-mail: sthom@smail.umaryland.edu. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2013.09.019.
Xu, Jiajun, Yang, Ming, Kosterin, Paul, Salzberg, Brian M., Milovanova, Tatyana N., Bhopale, Veena M., & Thom, Stephen R., E-mail: sthom@smail.umaryland.edu. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction. United States. doi:10.1016/J.TAAP.2013.09.019.
Xu, Jiajun, Yang, Ming, Kosterin, Paul, Salzberg, Brian M., Milovanova, Tatyana N., Bhopale, Veena M., and Thom, Stephen R., E-mail: sthom@smail.umaryland.edu. Sun . "Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction". United States. doi:10.1016/J.TAAP.2013.09.019.
@article{osti_22285520,
title = {Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction},
author = {Xu, Jiajun and Yang, Ming and Kosterin, Paul and Salzberg, Brian M. and Milovanova, Tatyana N. and Bhopale, Veena M. and Thom, Stephen R., E-mail: sthom@smail.umaryland.edu},
abstractNote = {We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.},
doi = {10.1016/J.TAAP.2013.09.019},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 273,
place = {United States},
year = {2013},
month = {12}
}