M1 protein from Streptococcus pyogenes induces nitric oxidemediated vascular hyporesponsiveness to phenylephrine: Involvement of toll-like receptor activation.
Sigurdardottir, Thorgerdur LU ; Björck, Viveka LU ; Herwald, Heiko LU
; Mörgelin, Matthias
LU
; RUTARDOTTIR, SIGURBJÖRG
LU
; Törnebrant, Johan
LU
and Bodelsson, Mikael
LU
(2010)
In Shock
34(1).
p.98-104
- Abstract
- Streptococcus pyogenes carrying M1 protein causes the severe and increasingly prevalent streptococcal toxic shock syndrome and necrotizing fasciitis. M1 protein is an important virulence factor of Streptococcus pyogenes and induces an inflammatory response in human monocytes. We wanted to investigate if purified M1 protein in solution could induce vascular nitric oxide (NO) production leading to vasopressor hyporesponsiveness. Rat aorta segments were incubated with M1 protein or lipopolysaccharide (LPS) in vitro. M1 protein (10 mug ml) and LPS (1 ng ml) to a similar extent induced NO production and hyporesponsiveness to the vasoconstrictor phenylephrine. Immuno-gold electron microscopy demonstrated that M1 protein binds to toll-like... (More)
- Streptococcus pyogenes carrying M1 protein causes the severe and increasingly prevalent streptococcal toxic shock syndrome and necrotizing fasciitis. M1 protein is an important virulence factor of Streptococcus pyogenes and induces an inflammatory response in human monocytes. We wanted to investigate if purified M1 protein in solution could induce vascular nitric oxide (NO) production leading to vasopressor hyporesponsiveness. Rat aorta segments were incubated with M1 protein or lipopolysaccharide (LPS) in vitro. M1 protein (10 mug ml) and LPS (1 ng ml) to a similar extent induced NO production and hyporesponsiveness to the vasoconstrictor phenylephrine. Immuno-gold electron microscopy demonstrated that M1 protein binds to toll-like receptor (TLR) 2 as well as TLR4 in mouse aorta but only to TLR2 in human omental artery. Incubation with M1 protein caused a reduction in the contractile response to phenylephrine in aorta segments from wild type and TLR2 knockout but not from TLR4 knockout mice. In conclusion, M1 protein causes vascular NO production leading to hyporesponsiveness to vasopressors via a mechanism involving TLR but the subtypes may be species-dependent. M1 protein could contribute to the circulatory disturbances accompanying severe invasive streptococcal infections. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1523759
- author
- Sigurdardottir, Thorgerdur
LU
; Björck, Viveka
LU
; Herwald, Heiko
LU
; Mörgelin, Matthias
LU
; RUTARDOTTIR, SIGURBJÖRG
LU
; Törnebrant, Johan
LU
and Bodelsson, Mikael
LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- circulation, Adrenoceptor, knockout mice, sepsis, serotype, shock, TLR, vasopressor
- in
- Shock
- volume
- 34
- issue
- 1
- pages
- 98 - 104
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000279024500016
- pmid:19997045
- scopus:77953879303
- ISSN
- 1540-0514
- DOI
- 10.1097/SHK.0b013e3181cdc50f
- language
- English
- LU publication?
- yes
- id
- febbe84b-17b0-4ae1-a91f-c6dcecdab738 (old id 1523759)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19997045?dopt=Abstract
- date added to LUP
- 2016-04-01 10:46:26
- date last changed
- 2022-01-26 02:21:16
@article{febbe84b-17b0-4ae1-a91f-c6dcecdab738,
abstract = {{Streptococcus pyogenes carrying M1 protein causes the severe and increasingly prevalent streptococcal toxic shock syndrome and necrotizing fasciitis. M1 protein is an important virulence factor of Streptococcus pyogenes and induces an inflammatory response in human monocytes. We wanted to investigate if purified M1 protein in solution could induce vascular nitric oxide (NO) production leading to vasopressor hyporesponsiveness. Rat aorta segments were incubated with M1 protein or lipopolysaccharide (LPS) in vitro. M1 protein (10 mug ml) and LPS (1 ng ml) to a similar extent induced NO production and hyporesponsiveness to the vasoconstrictor phenylephrine. Immuno-gold electron microscopy demonstrated that M1 protein binds to toll-like receptor (TLR) 2 as well as TLR4 in mouse aorta but only to TLR2 in human omental artery. Incubation with M1 protein caused a reduction in the contractile response to phenylephrine in aorta segments from wild type and TLR2 knockout but not from TLR4 knockout mice. In conclusion, M1 protein causes vascular NO production leading to hyporesponsiveness to vasopressors via a mechanism involving TLR but the subtypes may be species-dependent. M1 protein could contribute to the circulatory disturbances accompanying severe invasive streptococcal infections.}},
author = {{Sigurdardottir, Thorgerdur and Björck, Viveka and Herwald, Heiko and Mörgelin, Matthias and RUTARDOTTIR, SIGURBJÖRG and Törnebrant, Johan and Bodelsson, Mikael}},
issn = {{1540-0514}},
keywords = {{circulation; Adrenoceptor; knockout mice; sepsis; serotype; shock; TLR; vasopressor}},
language = {{eng}},
number = {{1}},
pages = {{98--104}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Shock}},
title = {{M1 protein from Streptococcus pyogenes induces nitric oxidemediated vascular hyporesponsiveness to phenylephrine: Involvement of toll-like receptor activation.}},
url = {{http://dx.doi.org/10.1097/SHK.0b013e3181cdc50f}},
doi = {{10.1097/SHK.0b013e3181cdc50f}},
volume = {{34}},
year = {{2010}},
}