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Bactericidal/permeability-increasing protein inhibits endotoxin-induced vascular nitric oxide synthesis.

Ciornei, Cristina LU ; Egesten, Arne LU ; Engström, Martin LU ; Törnebrandt, K and Bodelsson, Mikael LU (2002) In Acta Anaesthesiologica Scandinavica 46(9). p.1111-1118
Abstract
BACKGROUND: Endotoxin (lipopolysaccharide, LPS) up-regulates inducible nitric oxide synthase (iNOS) in blood vessels during septic shock. This promotes the production of nitric oxide (NO), leading to dilation of the vessels. The aim of the study was to investigate the effects of the LPS-binding endogenous antibiotic bactericidal/permeability-increasing protein (BPI) on the action of LPS on the blood vessels wall and to identify possible influence on underlying NO-related mechanisms. METHODS: Isolated segments of rat thoracic aorta and cultured primary smooth muscle cells were incubated for 5-48 h in the presence of the following combinations of compounds: (a) LPS; (b) interleukin-1beta (IL-1beta); (c) BPI; (d) BPI + LPS; (e) BPI + IL-1beta... (More)
BACKGROUND: Endotoxin (lipopolysaccharide, LPS) up-regulates inducible nitric oxide synthase (iNOS) in blood vessels during septic shock. This promotes the production of nitric oxide (NO), leading to dilation of the vessels. The aim of the study was to investigate the effects of the LPS-binding endogenous antibiotic bactericidal/permeability-increasing protein (BPI) on the action of LPS on the blood vessels wall and to identify possible influence on underlying NO-related mechanisms. METHODS: Isolated segments of rat thoracic aorta and cultured primary smooth muscle cells were incubated for 5-48 h in the presence of the following combinations of compounds: (a) LPS; (b) interleukin-1beta (IL-1beta); (c) BPI; (d) BPI + LPS; (e) BPI + IL-1beta or (f) neither BPI, LPS nor IL-1beta (control). After incubation of intact segments, we measured smooth muscle contraction in response to phenylephrine and accumulation of the NO end products nitrate and nitrite in surrounding medium. Western blot was used to assess the levels of inducible nitric oxide synthase (iNOS) in cultured cells. RESULTS: Both LPS and IL-1beta decreased contractility and increased NO production, as well as iNOS. Co-incubation with BPI attenuated all the effects of LPS but only the effects of prolonged exposure to IL-1beta in cultured cells. CONCLUSION: We conclude that BPI attenuates the LPS-induced changes in vascular reactivity by inhibiting the expression of iNOS resulting in decreased NO formation and restored responsiveness to vasoconstrictors. The data suggest that BPI can prevent circulatory disturbances during Gram-negative sepsis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Anaesthesiologica Scandinavica
volume
46
issue
9
pages
1111 - 1118
publisher
Wiley-Blackwell
external identifiers
  • wos:000178337800009
  • pmid:12366506
  • scopus:0036785329
ISSN
0001-5172
DOI
10.1034/j.1399-6576.2002.460909.x
language
English
LU publication?
yes
id
290163b4-d0d5-49b6-9998-71cc08db74ab (old id 110759)
alternative location
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12366506&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
date added to LUP
2007-06-27 15:42:31
date last changed
2017-02-26 03:35:03
@article{290163b4-d0d5-49b6-9998-71cc08db74ab,
  abstract     = {BACKGROUND: Endotoxin (lipopolysaccharide, LPS) up-regulates inducible nitric oxide synthase (iNOS) in blood vessels during septic shock. This promotes the production of nitric oxide (NO), leading to dilation of the vessels. The aim of the study was to investigate the effects of the LPS-binding endogenous antibiotic bactericidal/permeability-increasing protein (BPI) on the action of LPS on the blood vessels wall and to identify possible influence on underlying NO-related mechanisms. METHODS: Isolated segments of rat thoracic aorta and cultured primary smooth muscle cells were incubated for 5-48 h in the presence of the following combinations of compounds: (a) LPS; (b) interleukin-1beta (IL-1beta); (c) BPI; (d) BPI + LPS; (e) BPI + IL-1beta or (f) neither BPI, LPS nor IL-1beta (control). After incubation of intact segments, we measured smooth muscle contraction in response to phenylephrine and accumulation of the NO end products nitrate and nitrite in surrounding medium. Western blot was used to assess the levels of inducible nitric oxide synthase (iNOS) in cultured cells. RESULTS: Both LPS and IL-1beta decreased contractility and increased NO production, as well as iNOS. Co-incubation with BPI attenuated all the effects of LPS but only the effects of prolonged exposure to IL-1beta in cultured cells. CONCLUSION: We conclude that BPI attenuates the LPS-induced changes in vascular reactivity by inhibiting the expression of iNOS resulting in decreased NO formation and restored responsiveness to vasoconstrictors. The data suggest that BPI can prevent circulatory disturbances during Gram-negative sepsis.},
  author       = {Ciornei, Cristina and Egesten, Arne and Engström, Martin and Törnebrandt, K and Bodelsson, Mikael},
  issn         = {0001-5172},
  language     = {eng},
  number       = {9},
  pages        = {1111--1118},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Anaesthesiologica Scandinavica},
  title        = {Bactericidal/permeability-increasing protein inhibits endotoxin-induced vascular nitric oxide synthesis.},
  url          = {http://dx.doi.org/10.1034/j.1399-6576.2002.460909.x},
  volume       = {46},
  year         = {2002},
}