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Rac1 regulates sepsis-induced formation of platelet-derived microparticles and thrombin generation

Wang, Yongzhi LU ; Luo, Ling Tao LU ; Mörgelin, Matthias LU and Thorlacius, Henrik LU (2017) In Biochemical and Biophysical Research Communications 487(4). p.887-891
Abstract

Dysfunctional coagulation aggravates clinical outcome in patients with sepsis. The aim of this study was to define the role of Rac-1 in the formation of platelet-derived microparticles (PMPs) and thrombin generation (TG) in abdominal sepsis. Male C57BL/6 mice underwent cecal ligation and puncture (CLP). Scanning electron microscopy and flow cytometry were used to quantify PMPs. TG was determined by use of a fluorimetric assay. It was found that CLP increased Rac1 activity in platelets, which was abolished by administration of the Rac1 inhibitor NSC23766. Sepsis-induced TG in vivo was reflected by reduced capacity of plasma from septic animals to generate thrombin ex vivo. Administration of NSC23766 increased peak and total TG in plasma... (More)

Dysfunctional coagulation aggravates clinical outcome in patients with sepsis. The aim of this study was to define the role of Rac-1 in the formation of platelet-derived microparticles (PMPs) and thrombin generation (TG) in abdominal sepsis. Male C57BL/6 mice underwent cecal ligation and puncture (CLP). Scanning electron microscopy and flow cytometry were used to quantify PMPs. TG was determined by use of a fluorimetric assay. It was found that CLP increased Rac1 activity in platelets, which was abolished by administration of the Rac1 inhibitor NSC23766. Sepsis-induced TG in vivo was reflected by reduced capacity of plasma from septic animals to generate thrombin ex vivo. Administration of NSC23766 increased peak and total TG in plasma from CLP mice indicating that Rac-1 regulates sepsis-induced formation of thrombin. The number of circulating PMPs was markedly elevated in animals with abdominal sepsis. Treatment with NSC23766 significantly decreased formation of PMPs in septic mice. Platelet activation in vitro caused release of numerous MPs. Notably, NSC23766 abolished PMP formation in activated platelets in vitro. These findings suggest that Rac-1 regulates PMP formation and TG in sepsis and that inhibition of Rac1 activity could be a useful target to inhibit dysfunctional coagulation in abdominal sepsis.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Coagulation, Inflammation, Microparticles, Platelets
in
Biochemical and Biophysical Research Communications
volume
487
issue
4
pages
5 pages
publisher
Elsevier
external identifiers
  • scopus:85019091841
  • wos:000401883700019
ISSN
0006-291X
DOI
10.1016/j.bbrc.2017.04.147
language
English
LU publication?
yes
id
6a6b84ae-647d-4be1-bb82-95a4f89269d6
date added to LUP
2017-05-29 14:07:47
date last changed
2017-09-18 11:37:56
@article{6a6b84ae-647d-4be1-bb82-95a4f89269d6,
  abstract     = {<p>Dysfunctional coagulation aggravates clinical outcome in patients with sepsis. The aim of this study was to define the role of Rac-1 in the formation of platelet-derived microparticles (PMPs) and thrombin generation (TG) in abdominal sepsis. Male C57BL/6 mice underwent cecal ligation and puncture (CLP). Scanning electron microscopy and flow cytometry were used to quantify PMPs. TG was determined by use of a fluorimetric assay. It was found that CLP increased Rac1 activity in platelets, which was abolished by administration of the Rac1 inhibitor NSC23766. Sepsis-induced TG in vivo was reflected by reduced capacity of plasma from septic animals to generate thrombin ex vivo. Administration of NSC23766 increased peak and total TG in plasma from CLP mice indicating that Rac-1 regulates sepsis-induced formation of thrombin. The number of circulating PMPs was markedly elevated in animals with abdominal sepsis. Treatment with NSC23766 significantly decreased formation of PMPs in septic mice. Platelet activation in vitro caused release of numerous MPs. Notably, NSC23766 abolished PMP formation in activated platelets in vitro. These findings suggest that Rac-1 regulates PMP formation and TG in sepsis and that inhibition of Rac1 activity could be a useful target to inhibit dysfunctional coagulation in abdominal sepsis.</p>},
  author       = {Wang, Yongzhi and Luo, Ling Tao and Mörgelin, Matthias and Thorlacius, Henrik},
  issn         = {0006-291X},
  keyword      = {Coagulation,Inflammation,Microparticles,Platelets},
  language     = {eng},
  month        = {06},
  number       = {4},
  pages        = {887--891},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Rac1 regulates sepsis-induced formation of platelet-derived microparticles and thrombin generation},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2017.04.147},
  volume       = {487},
  year         = {2017},
}