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M1 protein from streptococcus pyogenes induces nitric oxide-mediated vascular hyporesponsiveness to phenylephrine:

Thorgerdur Sigurdardottir1, Viveka Björck, Heiko Herwald

  • 1Division of Anesthesiology and Intensive Care, Department of Clinical Sciences, Lund University, Lund, Sweden.

Shock (Augusta, Ga.)
|December 10, 2009
PubMed

Insights

Streptococcus pyogenes M1 protein triggers nitric oxide production, causing blood vessel hyporesponsiveness. This mechanism, involving Toll-like receptors, contributes to severe invasive streptococcal infections.

Area of Science:

  • Immunology
  • Vascular Biology
  • Microbiology

Background:

  • Streptococcus pyogenes M1 protein is a key virulence factor in severe infections like toxic shock syndrome.
  • M1 protein induces inflammatory responses in human monocytes.
  • The role of M1 protein in vascular dysfunction and nitric oxide (NO) production remains unclear.

Purpose of the Study:

  • To investigate if purified M1 protein induces vascular NO production and vasopressor hyporesponsiveness.
  • To explore the involvement of Toll-like receptors (TLRs) in M1 protein-mediated vascular effects.

Main Methods:

  • Rat aortic segments were incubated with purified M1 protein or lipopolysaccharide (LPS) in vitro.
  • Nitric oxide (NO) production and contractile responses to phenylephrine were measured.
  • Immunogold electron microscopy identified M1 protein binding to TLRs in mouse aorta and human arteries.
  • Experiments utilized wild-type, TLR2-knockout, and TLR4-knockout mice.

Main Results:

  • M1 protein induced NO production and hyporesponsiveness to phenylephrine, similar to LPS.
  • M1 protein bound to Toll-like receptor 2 (TLR2) and TLR4 in mouse aorta, and TLR2 in human omental arteries.
  • M1 protein reduced contractile responses in wild-type and TLR2-knockout aortic segments, but not in TLR4-knockout segments.

Conclusions:

  • M1 protein induces vascular NO production and hyporesponsiveness to vasopressors via TLR-dependent mechanisms.
  • The specific TLR subtypes involved in M1 protein's vascular effects appear to be species-dependent.
  • M1 protein likely contributes to circulatory disturbances in severe invasive streptococcal infections.

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