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Streptococcal M1 protein induces hyporesponsiveness and cytokine release from human arteries in a fibrinogen-dependent manner : A translational study

Björck, Viveka LU ; Påhlman, Lisa I. LU ; Törnebrant, Johan LU and Bodelsson, Mikael LU (2018) In Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 26(1).
Abstract

Background: Streptococcus pyogenes is a Gram positive bacterial species commonly involved in sepsis. Invasive strains express virulence factors such as the M1 protein. M1 protein forms complexes with fibrinogen leading to a cytokine storm in plasma contributing to the development of septic shock and organ failure. In experimental animals M1 protein causes vascular nitric oxide production and hyporesponsiveness to pressors, but it is not known whether it affects the human vascular wall. Methods: Human omental arteries obtained during surgery were incubated in vitro with M1 protein or lipopolysaccharide (LPS) as positive control, with or without plasma. After 48h, contractile response to noradrenaline was measured, and levels of... (More)

Background: Streptococcus pyogenes is a Gram positive bacterial species commonly involved in sepsis. Invasive strains express virulence factors such as the M1 protein. M1 protein forms complexes with fibrinogen leading to a cytokine storm in plasma contributing to the development of septic shock and organ failure. In experimental animals M1 protein causes vascular nitric oxide production and hyporesponsiveness to pressors, but it is not known whether it affects the human vascular wall. Methods: Human omental arteries obtained during surgery were incubated in vitro with M1 protein or lipopolysaccharide (LPS) as positive control, with or without plasma. After 48h, contractile response to noradrenaline was measured, and levels of nitrite/nitrate and the cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in the incubation medium were measured. A second set of arteries were incubated with or without main components of plasma (immunoglobulin G, albumin or fibrinogen), in the presence of M1 protein followed by cytokine measurement. Results: Artery segments incubated with M1 protein and plasma contracted weaker in response to noradrenaline, and levels of IL-6 and IL-8 were significantly higher compared to after incubation with M1 protein alone. Incubation with M1 protein and fibrinogen resulted in elevated levels of IL-6 and IL-8, while incubation with M1 protein and albumin or immunoglobulin G did not affect the levels. Neither any of the other cytokines nor nitrite/nitrate was detected in the medium in any of the incubation conditions. Conclusions: The study shows that M1 protein of Streptococcus pyogenes has a direct effect on the human vascular wall in the presence of plasma, demonstrated both as a diminished contractile response to noradrenaline and increased cytokine production. The effect of plasma was attributed to fibrinogen. The findings suggest that M1 protein contributes to the development of septic shock through impairment of the contractility of the vascular wall.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Artery, Cytokine, Fibrinogen, Hypotension, Interleukin, M1 protein, Sepsis, Streptococcus
in
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
volume
26
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85050332632
ISSN
1757-7241
DOI
10.1186/s13049-018-0530-1
language
English
LU publication?
yes
id
ca645800-3944-4db8-9d5c-0b5c60640a63
date added to LUP
2018-08-20 10:22:40
date last changed
2019-01-06 14:02:17
@article{ca645800-3944-4db8-9d5c-0b5c60640a63,
  abstract     = {<p>Background: Streptococcus pyogenes is a Gram positive bacterial species commonly involved in sepsis. Invasive strains express virulence factors such as the M1 protein. M1 protein forms complexes with fibrinogen leading to a cytokine storm in plasma contributing to the development of septic shock and organ failure. In experimental animals M1 protein causes vascular nitric oxide production and hyporesponsiveness to pressors, but it is not known whether it affects the human vascular wall. Methods: Human omental arteries obtained during surgery were incubated in vitro with M1 protein or lipopolysaccharide (LPS) as positive control, with or without plasma. After 48h, contractile response to noradrenaline was measured, and levels of nitrite/nitrate and the cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in the incubation medium were measured. A second set of arteries were incubated with or without main components of plasma (immunoglobulin G, albumin or fibrinogen), in the presence of M1 protein followed by cytokine measurement. Results: Artery segments incubated with M1 protein and plasma contracted weaker in response to noradrenaline, and levels of IL-6 and IL-8 were significantly higher compared to after incubation with M1 protein alone. Incubation with M1 protein and fibrinogen resulted in elevated levels of IL-6 and IL-8, while incubation with M1 protein and albumin or immunoglobulin G did not affect the levels. Neither any of the other cytokines nor nitrite/nitrate was detected in the medium in any of the incubation conditions. Conclusions: The study shows that M1 protein of Streptococcus pyogenes has a direct effect on the human vascular wall in the presence of plasma, demonstrated both as a diminished contractile response to noradrenaline and increased cytokine production. The effect of plasma was attributed to fibrinogen. The findings suggest that M1 protein contributes to the development of septic shock through impairment of the contractility of the vascular wall.</p>},
  articleno    = {61},
  author       = {Björck, Viveka and Påhlman, Lisa I. and Törnebrant, Johan and Bodelsson, Mikael},
  issn         = {1757-7241},
  keyword      = {Artery,Cytokine,Fibrinogen,Hypotension,Interleukin,M1 protein,Sepsis,Streptococcus},
  language     = {eng},
  month        = {07},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine},
  title        = {Streptococcal M1 protein induces hyporesponsiveness and cytokine release from human arteries in a fibrinogen-dependent manner : A translational study},
  url          = {http://dx.doi.org/10.1186/s13049-018-0530-1},
  volume       = {26},
  year         = {2018},
}