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Signaling mechanisms in Streptococcal M1 proteininduced inflammation and injury in the lung

Zhang, Songen LU (2012) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2012:104.
Abstract
Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections.

Acute lung injury is recognized as a key component in the pathophysiology of streptococcal M1 proteininduced

inflammation. Numerous reports have demonstrated that excessive infiltration of neutrophils is a

rate-limiting step in septic lung damage. We observed that targeting neutrophil functions appeared more

relevant than inhibiting platelet activation in severe infections triggered by streptococcal M1 protein. In study

II, it was shown that simvastatin was a powerful inhibitor of neutrophil infiltration in acute lung damage

triggered by streptococcal M1 protein. The inhibitory... (More)
Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections.

Acute lung injury is recognized as a key component in the pathophysiology of streptococcal M1 proteininduced

inflammation. Numerous reports have demonstrated that excessive infiltration of neutrophils is a

rate-limiting step in septic lung damage. We observed that targeting neutrophil functions appeared more

relevant than inhibiting platelet activation in severe infections triggered by streptococcal M1 protein. In study

II, it was shown that simvastatin was a powerful inhibitor of neutrophil infiltration in acute lung damage

triggered by streptococcal M1 protein. The inhibitory effect of simvastatin on M1 protein-induced neutrophil

recruitment appeared related to reduced pulmonary generation of CXC chemokines. Following the mevalonate

signaling pathway, checking downstream effectors, both Rho/Rho Kinase and p38 MAPK signaling pathway

played critical roles in M1 protein-induced lung recruitment of neutrophils via formation of CXC chemokines

and Mac-1 expression. In addition, our findings also suggested that farnesyltransferase was a potent regulator

of CXC chemokine formation in alveolar macrophages and that inhibition of farnesyltransferase not only

reduces neutrophil recruitment but also attenuates acute lung injury provoked by streptococcal M1 protein.

Thus, these new data may provide a basis for the development of more specific and effective treatment of

patients with STSS. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Sund, Malin, Department of Surgical and Perioperative Sciences,University of Umeå, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2012:104
pages
72 pages
publisher
Surgery Research Unit, Clinical Science, Malmö
defense location
CRC Aula, Entrance 72, Skåne University Hospital, Malmö
defense date
2012-11-30 13:00
ISSN
1652-8220
ISBN
978-91-87189-67-8
language
English
LU publication?
yes
id
64c8150d-815f-4718-8292-4be0d0085e27 (old id 3164132)
date added to LUP
2012-11-06 12:20:03
date last changed
2016-09-19 08:44:46
@phdthesis{64c8150d-815f-4718-8292-4be0d0085e27,
  abstract     = {Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections.<br/><br>
Acute lung injury is recognized as a key component in the pathophysiology of streptococcal M1 proteininduced<br/><br>
inflammation. Numerous reports have demonstrated that excessive infiltration of neutrophils is a<br/><br>
rate-limiting step in septic lung damage. We observed that targeting neutrophil functions appeared more<br/><br>
relevant than inhibiting platelet activation in severe infections triggered by streptococcal M1 protein. In study<br/><br>
II, it was shown that simvastatin was a powerful inhibitor of neutrophil infiltration in acute lung damage<br/><br>
triggered by streptococcal M1 protein. The inhibitory effect of simvastatin on M1 protein-induced neutrophil<br/><br>
recruitment appeared related to reduced pulmonary generation of CXC chemokines. Following the mevalonate<br/><br>
signaling pathway, checking downstream effectors, both Rho/Rho Kinase and p38 MAPK signaling pathway<br/><br>
played critical roles in M1 protein-induced lung recruitment of neutrophils via formation of CXC chemokines<br/><br>
and Mac-1 expression. In addition, our findings also suggested that farnesyltransferase was a potent regulator<br/><br>
of CXC chemokine formation in alveolar macrophages and that inhibition of farnesyltransferase not only<br/><br>
reduces neutrophil recruitment but also attenuates acute lung injury provoked by streptococcal M1 protein.<br/><br>
Thus, these new data may provide a basis for the development of more specific and effective treatment of<br/><br>
patients with STSS.},
  author       = {Zhang, Songen},
  isbn         = {978-91-87189-67-8},
  issn         = {1652-8220},
  language     = {eng},
  pages        = {72},
  publisher    = {Surgery Research Unit, Clinical Science, Malmö},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Signaling mechanisms in Streptococcal M1 proteininduced inflammation and injury in the lung},
  volume       = {2012:104},
  year         = {2012},
}