M1 protein from Streptococcus pyogenes induces nitric oxidemediated vascular hyporesponsiveness to phenylephrine: Involvement of toll-like receptor activation.

Thorgerdur Sigurdardottir, Viveka Björck, Heiko Herwald, Matthias Mörgelin, SIGURBJÖRG RUTARDOTTIR, Johan Törnebrant, Mikael Bodelsson

Research output: Contribution to journalArticlepeer-review

10 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)98-104
JournalShock
Volume34
Issue number1
DOIs
Publication statusPublished - 2010

Subject classification (UKÄ)

  • Infectious Medicine
  • Anesthesiology and Intensive Care

Keywords

  • circulation
  • Adrenoceptor
  • knockout mice
  • sepsis
  • serotype
  • shock
  • TLR
  • vasopressor

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