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STREPTOCOCCAL M1 PROTEIN-INDUCED LUNG INJURY IS INDEPENDENT OF PLATELETS IN MICE.

Zhang, Su LU ; Zhang, Songen LU ; Rahman, Milladur LU ; Herwald, Heiko LU and Thorlacius, Henrik LU (2011) In Shock Jul 1. p.86-91
Abstract
Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections. M1 protein challenge can cause widespread microthrombosis, suggesting a role of platelets in streptococcal sepsis. Herein, we hypothesized that platelets may play a role in M1 protein-induced lung inflammation and injury. M1 protein was injected intravenously in C57Bl/6 mice. For platelet and neutrophil depletion, an anti-GP1balpha antibody and an anti-Gr-1 antibody, respectively, were administered prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for analysis of neutrophil infiltration, edema and macrophage inflammatory protein-2 (MIP-2) formation. Blood was collected for analysis of membrane-activated... (More)
Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections. M1 protein challenge can cause widespread microthrombosis, suggesting a role of platelets in streptococcal sepsis. Herein, we hypothesized that platelets may play a role in M1 protein-induced lung inflammation and injury. M1 protein was injected intravenously in C57Bl/6 mice. For platelet and neutrophil depletion, an anti-GP1balpha antibody and an anti-Gr-1 antibody, respectively, were administered prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for analysis of neutrophil infiltration, edema and macrophage inflammatory protein-2 (MIP-2) formation. Blood was collected for analysis of membrane-activated complex-1 (Mac-1) and CD40 ligand (CD40L) expression on neutrophils and platelets as well as soluble CD40L in plasma. M1 protein caused significant pulmonary damage characterized by neutrophil infiltration, increased formation of edema and MIP-2 in the lung as well as enhanced Mac-1 expression on neutrophils. However, M1 protein challenge had no effect on platelet surface expression of CD40L or soluble CD40L levels in plasma. Interestingly, platelet depletion had no influence on M1 protein-induced neutrophil recruitment, MIP-2 production and tissue damage in the lung or Mac-1 expression on neutrophils. Moreover, we observed that M1 protein could bind to neutrophils but not to platelets. On the other hand, neutrophil depletion abolished M1 protein-induced edema formation and tissue damage in the lung. Our data suggest that neutrophils but not platelets are involved in the pathophysiology of M1 protein-provoked pulmonary damage. Thus, neutrophils may constitute a key target in infections caused by Streptococcus pyogenes of the M1 serotype. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Shock
volume
Jul 1
pages
86 - 91
publisher
BioMedical Press
external identifiers
  • wos:000285381500014
  • pmid:20577151
  • scopus:78650770417
ISSN
1540-0514
DOI
10.1097/SHK.0b013e3181ea4476
language
English
LU publication?
yes
id
1ec83450-17a9-44c3-b978-32096be3e1a4 (old id 1625720)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20577151?dopt=Abstract
date added to LUP
2010-07-01 22:52:12
date last changed
2017-01-01 07:37:22
@article{1ec83450-17a9-44c3-b978-32096be3e1a4,
  abstract     = {Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections. M1 protein challenge can cause widespread microthrombosis, suggesting a role of platelets in streptococcal sepsis. Herein, we hypothesized that platelets may play a role in M1 protein-induced lung inflammation and injury. M1 protein was injected intravenously in C57Bl/6 mice. For platelet and neutrophil depletion, an anti-GP1balpha antibody and an anti-Gr-1 antibody, respectively, were administered prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for analysis of neutrophil infiltration, edema and macrophage inflammatory protein-2 (MIP-2) formation. Blood was collected for analysis of membrane-activated complex-1 (Mac-1) and CD40 ligand (CD40L) expression on neutrophils and platelets as well as soluble CD40L in plasma. M1 protein caused significant pulmonary damage characterized by neutrophil infiltration, increased formation of edema and MIP-2 in the lung as well as enhanced Mac-1 expression on neutrophils. However, M1 protein challenge had no effect on platelet surface expression of CD40L or soluble CD40L levels in plasma. Interestingly, platelet depletion had no influence on M1 protein-induced neutrophil recruitment, MIP-2 production and tissue damage in the lung or Mac-1 expression on neutrophils. Moreover, we observed that M1 protein could bind to neutrophils but not to platelets. On the other hand, neutrophil depletion abolished M1 protein-induced edema formation and tissue damage in the lung. Our data suggest that neutrophils but not platelets are involved in the pathophysiology of M1 protein-provoked pulmonary damage. Thus, neutrophils may constitute a key target in infections caused by Streptococcus pyogenes of the M1 serotype.},
  author       = {Zhang, Su and Zhang, Songen and Rahman, Milladur and Herwald, Heiko and Thorlacius, Henrik},
  issn         = {1540-0514},
  language     = {eng},
  pages        = {86--91},
  publisher    = {BioMedical Press},
  series       = {Shock},
  title        = {STREPTOCOCCAL M1 PROTEIN-INDUCED LUNG INJURY IS INDEPENDENT OF PLATELETS IN MICE.},
  url          = {http://dx.doi.org/10.1097/SHK.0b013e3181ea4476},
  volume       = {Jul 1},
  year         = {2011},
}