Heparin-binding protein (HBP/CAP37) - a link to endothelin-1 in endotoxemia-induced pulmonary oedema?
Persson, B. P. ; Halldorsdottir, H. ; Lindbom, L. ; Rossi, P. ; Herwald, Heiko LU
; Weitzberg, E.
and Oldner, A.
(2014)
In Acta Anaesthesiologica Scandinavica
58(5).
p.549-559
- Abstract
- BackgroundVascular leakage and oedema formation are key components in sepsis. In septic patients, plasma levels of the vasoconstrictive and pro-inflammatory peptide endothelin-1 (ET-1) correlate with mortality. During sepsis, neutrophils release heparin-binding protein (HBP) known to increase vascular permeability and to be a promising biomarker of human sepsis. As disruption of ET-signalling in endotoxemia attenuates formation of oedema, we hypothesized that this effect could be related to decreased levels of HBP. To investigate this, we studied the effects of ET-receptor antagonism on plasma HBP and oedema formation in a porcine model of sepsis. In addition, to further characterize a potential endothelin/HBP interaction, we investigated... (More)
- BackgroundVascular leakage and oedema formation are key components in sepsis. In septic patients, plasma levels of the vasoconstrictive and pro-inflammatory peptide endothelin-1 (ET-1) correlate with mortality. During sepsis, neutrophils release heparin-binding protein (HBP) known to increase vascular permeability and to be a promising biomarker of human sepsis. As disruption of ET-signalling in endotoxemia attenuates formation of oedema, we hypothesized that this effect could be related to decreased levels of HBP. To investigate this, we studied the effects of ET-receptor antagonism on plasma HBP and oedema formation in a porcine model of sepsis. In addition, to further characterize a potential endothelin/HBP interaction, we investigated the effects of graded ET-receptor agonist infusions. MethodsSixteen anesthetized pigs were subjected to 5h of endotoxemia and were randomized to receive either the ET-receptor antagonist tezosentan or vehicle after 2h. Haemodynamics, gas-exchange and lung water were monitored. In separate experiments, plasma HBP was measured in eight non-endotoxemic animals exposed to graded infusion of ET-1 or sarafotoxin 6c. ResultsEndotoxemia increased plasma ET-1, plasma HBP, and extravascular lung water. Tezosentan-treatment markedly attenuated plasma HBP and extravascular lung water, and these parameters correlated significantly. Tezosentan decreased pulmonary vascular resistance and increased respiratory compliance. In non-endotoxemic pigs graded ET-1 and sarafotoxin 6c infusions caused a dose-dependent increase in plasma HBP. ConclusionsET-receptor antagonism reduces porcine endotoxin-induced pulmonary oedema and plasma levels of the oedema-promoting protein HBP. Moreover, direct ET-receptor stimulation distinctively increases plasma HBP. Together, these results suggest a novel mechanism by which ET-1 contributes to formation of oedema during experimental sepsis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4559105
- author
- Persson, B. P.
; Halldorsdottir, H.
; Lindbom, L.
; Rossi, P.
; Herwald, Heiko
LU
; Weitzberg, E.
and Oldner, A.
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Acta Anaesthesiologica Scandinavica
- volume
- 58
- issue
- 5
- pages
- 549 - 559
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000334269600006
- scopus:84898803738
- pmid:24611481
- ISSN
- 0001-5172
- DOI
- 10.1111/aas.12301
- language
- English
- LU publication?
- yes
- id
- dfe605d8-e876-47aa-969a-6bb6b511f432 (old id 4559105)
- date added to LUP
- 2016-04-01 10:23:19
- date last changed
- 2022-03-04 19:02:55
@article{dfe605d8-e876-47aa-969a-6bb6b511f432,
abstract = {{BackgroundVascular leakage and oedema formation are key components in sepsis. In septic patients, plasma levels of the vasoconstrictive and pro-inflammatory peptide endothelin-1 (ET-1) correlate with mortality. During sepsis, neutrophils release heparin-binding protein (HBP) known to increase vascular permeability and to be a promising biomarker of human sepsis. As disruption of ET-signalling in endotoxemia attenuates formation of oedema, we hypothesized that this effect could be related to decreased levels of HBP. To investigate this, we studied the effects of ET-receptor antagonism on plasma HBP and oedema formation in a porcine model of sepsis. In addition, to further characterize a potential endothelin/HBP interaction, we investigated the effects of graded ET-receptor agonist infusions. MethodsSixteen anesthetized pigs were subjected to 5h of endotoxemia and were randomized to receive either the ET-receptor antagonist tezosentan or vehicle after 2h. Haemodynamics, gas-exchange and lung water were monitored. In separate experiments, plasma HBP was measured in eight non-endotoxemic animals exposed to graded infusion of ET-1 or sarafotoxin 6c. ResultsEndotoxemia increased plasma ET-1, plasma HBP, and extravascular lung water. Tezosentan-treatment markedly attenuated plasma HBP and extravascular lung water, and these parameters correlated significantly. Tezosentan decreased pulmonary vascular resistance and increased respiratory compliance. In non-endotoxemic pigs graded ET-1 and sarafotoxin 6c infusions caused a dose-dependent increase in plasma HBP. ConclusionsET-receptor antagonism reduces porcine endotoxin-induced pulmonary oedema and plasma levels of the oedema-promoting protein HBP. Moreover, direct ET-receptor stimulation distinctively increases plasma HBP. Together, these results suggest a novel mechanism by which ET-1 contributes to formation of oedema during experimental sepsis.}},
author = {{Persson, B. P. and Halldorsdottir, H. and Lindbom, L. and Rossi, P. and Herwald, Heiko and Weitzberg, E. and Oldner, A.}},
issn = {{0001-5172}},
language = {{eng}},
number = {{5}},
pages = {{549--559}},
publisher = {{Wiley-Blackwell}},
series = {{Acta Anaesthesiologica Scandinavica}},
title = {{Heparin-binding protein (HBP/CAP37) - a link to endothelin-1 in endotoxemia-induced pulmonary oedema?}},
url = {{http://dx.doi.org/10.1111/aas.12301}},
doi = {{10.1111/aas.12301}},
volume = {{58}},
year = {{2014}},
}