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INCREASED LEVELS OF GLYCOSAMINOGLYCANS DURING SEPTIC SHOCK: RELATION TO MORTALITY AND THE ANTIBACTERIAL ACTIONS OF PLASMA.

Nelson, Axel; Berkestedt, Ingrid LU ; Schmidtchen, Artur LU ; Ljunggren, Lennart and Bodelsson, Mikael LU (2008) In Shock 30. p.623-627
Abstract
Glycosaminoglycans (GAGs) are structurally heterogeneous negatively charged polysaccharides. Endothelial GAGs, also known as glycocalyx, are involved in capillary permeability. In rat venules stimulated with proinflammatory substances ex vivo, the GAG-containing proteoglycan, syndecan-1, is shed from the endothelium. We wanted to investigate if we could trace the same response during septic shock as reflected in the circulating GAG levels. Arterial plasma samples were collected from 18 consecutive septic shock patients admitted to our intensive care unit. Plasma GAGs were measured with an Alcian blue slot binding assay, and syndecan-1 levels were measured with enzyme-linked immunosorbent assay. Effects of GAGs on the antibacterial activity... (More)
Glycosaminoglycans (GAGs) are structurally heterogeneous negatively charged polysaccharides. Endothelial GAGs, also known as glycocalyx, are involved in capillary permeability. In rat venules stimulated with proinflammatory substances ex vivo, the GAG-containing proteoglycan, syndecan-1, is shed from the endothelium. We wanted to investigate if we could trace the same response during septic shock as reflected in the circulating GAG levels. Arterial plasma samples were collected from 18 consecutive septic shock patients admitted to our intensive care unit. Plasma GAGs were measured with an Alcian blue slot binding assay, and syndecan-1 levels were measured with enzyme-linked immunosorbent assay. Effects of GAGs on the antibacterial activity of plasma were assessed by a radial diffusion assay. The median plasma GAG level was significantly higher in the septic shock patients than in matched controls (median [interquartile range], 2.7 mug/mL [1.9 - 4.8 mug/mL] vs. 1.8 mug/mL [1.7 - 2.0 mug/mL]). Furthermore, the GAG levels were significantly higher in nonsurvivors (4.6 mug/mL [3.1 - 8.8 mug/mL], n = 8) than survivors (1.8 mug/mL [1.6 - 2.6 mug/mL], n = 10). The syndecan-1 levels were also increased in the patients compared with controls (246 ng/mL [180 - 496 ng/mL] vs. 26 ng/mL [23 - 31 ng/mL]) and correlated to the cardiovascular Sequential Organ Failure Assessment score. The GAGs inhibited the endogenous antibacterial activity of plasma as well as isolated antimicrobial peptides. The concentrations required were in the same range as the GAG levels measured in the patients. These results show that the GAG levels are increased in septic shock patients, possibly reflecting peripheral endothelial cell damage. We also found that GAGs in relevant concentrations neutralize antimicrobial peptides in plasma. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Shock
volume
30
pages
623 - 627
publisher
BioMedical Press
external identifiers
  • wos:000261032600003
  • pmid:18497712
  • scopus:54849433850
ISSN
1540-0514
DOI
10.1097/SHK.0b013e3181777da3
language
English
LU publication?
yes
id
3eb1490b-2ef0-4039-9916-1cdc380aefac (old id 1153827)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18497712?dopt=Abstract
date added to LUP
2008-06-04 09:04:49
date last changed
2017-11-05 04:41:09
@article{3eb1490b-2ef0-4039-9916-1cdc380aefac,
  abstract     = {Glycosaminoglycans (GAGs) are structurally heterogeneous negatively charged polysaccharides. Endothelial GAGs, also known as glycocalyx, are involved in capillary permeability. In rat venules stimulated with proinflammatory substances ex vivo, the GAG-containing proteoglycan, syndecan-1, is shed from the endothelium. We wanted to investigate if we could trace the same response during septic shock as reflected in the circulating GAG levels. Arterial plasma samples were collected from 18 consecutive septic shock patients admitted to our intensive care unit. Plasma GAGs were measured with an Alcian blue slot binding assay, and syndecan-1 levels were measured with enzyme-linked immunosorbent assay. Effects of GAGs on the antibacterial activity of plasma were assessed by a radial diffusion assay. The median plasma GAG level was significantly higher in the septic shock patients than in matched controls (median [interquartile range], 2.7 mug/mL [1.9 - 4.8 mug/mL] vs. 1.8 mug/mL [1.7 - 2.0 mug/mL]). Furthermore, the GAG levels were significantly higher in nonsurvivors (4.6 mug/mL [3.1 - 8.8 mug/mL], n = 8) than survivors (1.8 mug/mL [1.6 - 2.6 mug/mL], n = 10). The syndecan-1 levels were also increased in the patients compared with controls (246 ng/mL [180 - 496 ng/mL] vs. 26 ng/mL [23 - 31 ng/mL]) and correlated to the cardiovascular Sequential Organ Failure Assessment score. The GAGs inhibited the endogenous antibacterial activity of plasma as well as isolated antimicrobial peptides. The concentrations required were in the same range as the GAG levels measured in the patients. These results show that the GAG levels are increased in septic shock patients, possibly reflecting peripheral endothelial cell damage. We also found that GAGs in relevant concentrations neutralize antimicrobial peptides in plasma.},
  author       = {Nelson, Axel and Berkestedt, Ingrid and Schmidtchen, Artur and Ljunggren, Lennart and Bodelsson, Mikael},
  issn         = {1540-0514},
  language     = {eng},
  pages        = {623--627},
  publisher    = {BioMedical Press},
  series       = {Shock},
  title        = {INCREASED LEVELS OF GLYCOSAMINOGLYCANS DURING SEPTIC SHOCK: RELATION TO MORTALITY AND THE ANTIBACTERIAL ACTIONS OF PLASMA.},
  url          = {http://dx.doi.org/10.1097/SHK.0b013e3181777da3},
  volume       = {30},
  year         = {2008},
}