Advanced

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:
author
organization
publishing date
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
BioMedical Press
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
2010-01-14 12:57:15
date last changed
2018-05-29 12:00:28
@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},
  keyword      = {circulation,Adrenoceptor,knockout mice,sepsis,serotype,shock,TLR,vasopressor},
  language     = {eng},
  number       = {1},
  pages        = {98--104},
  publisher    = {BioMedical Press},
  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},
  volume       = {34},
  year         = {2010},
}