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Central Role of Rho Kinase in Lipopolysaccharide-Induced Platelet Capture on Venous Endothelium.

Slotta, Jan; Braun, Oscar LU ; Menger, Michael and Thorlacius, Henrik LU (2008) In Journal of Investigative Medicine 56(4). p.720-725
Abstract
BACKGROUND:: Platelet-endothelial cell interactions play a key role in hemostasis and pathological coagulation and are dependent on different surface molecules that are expressed upon activation (eg, mediated by lipopolysaccharide [LPS]). Recently, we have shown that Rho kinase plays a central role in LPS-mediated leukocyte-endothelial cell interactions. We investigated the role of Rho-kinase in inflammatory interactions between platelets and the endothelium in femoral veins in vivo. METHODS:: Mice were injected intravenously with LPS (0.5 mg/kg)/D-galactosamine (900 mg/kg), and Rho kinase was blocked with fasudil 15 minutes before LPS application. Four hours after LPS administration, intravital fluorescence microscopy of the femoral vein... (More)
BACKGROUND:: Platelet-endothelial cell interactions play a key role in hemostasis and pathological coagulation and are dependent on different surface molecules that are expressed upon activation (eg, mediated by lipopolysaccharide [LPS]). Recently, we have shown that Rho kinase plays a central role in LPS-mediated leukocyte-endothelial cell interactions. We investigated the role of Rho-kinase in inflammatory interactions between platelets and the endothelium in femoral veins in vivo. METHODS:: Mice were injected intravenously with LPS (0.5 mg/kg)/D-galactosamine (900 mg/kg), and Rho kinase was blocked with fasudil 15 minutes before LPS application. Four hours after LPS administration, intravital fluorescence microscopy of the femoral vein was performed, and primary and secondary platelet-endothelial cell interactions were visualized after in vivo platelet staining with rhodamine 6G. RESULTS:: Intravital microscopy showed a significant increase in platelet tethering, rolling, and firm adhesion as well as platelet secondary capture in LPS-treated mice. Rho-kinase inhibition by fasudil significantly reduced platelet tethering, rolling, and firm adhesion. Interestingly, functional blockade of Rho kinase was also able to diminish secondary platelet capture by 79%. CONCLUSIONS:: From our data, we conclude that Rho-kinase signaling plays a central role in the regulation of LPS-induced platelet-endothelial cell interactions in large veins in vivo. Thus, Rho-kinase inhibition might be useful in prevention or treatment of pathological inflammation and endotoxin-mediated hypercoagulation. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Investigative Medicine
volume
56
issue
4
pages
720 - 725
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000254898200019
  • pmid:18382268
  • scopus:58149109322
ISSN
1708-8267
DOI
10.231/JIM.0b013e31816c3e81
language
English
LU publication?
yes
id
30086eab-7bd3-4559-9124-8faadfa74921 (old id 1147883)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18382268?dopt=Abstract
date added to LUP
2008-05-07 14:23:08
date last changed
2017-02-05 04:30:27
@article{30086eab-7bd3-4559-9124-8faadfa74921,
  abstract     = {BACKGROUND:: Platelet-endothelial cell interactions play a key role in hemostasis and pathological coagulation and are dependent on different surface molecules that are expressed upon activation (eg, mediated by lipopolysaccharide [LPS]). Recently, we have shown that Rho kinase plays a central role in LPS-mediated leukocyte-endothelial cell interactions. We investigated the role of Rho-kinase in inflammatory interactions between platelets and the endothelium in femoral veins in vivo. METHODS:: Mice were injected intravenously with LPS (0.5 mg/kg)/D-galactosamine (900 mg/kg), and Rho kinase was blocked with fasudil 15 minutes before LPS application. Four hours after LPS administration, intravital fluorescence microscopy of the femoral vein was performed, and primary and secondary platelet-endothelial cell interactions were visualized after in vivo platelet staining with rhodamine 6G. RESULTS:: Intravital microscopy showed a significant increase in platelet tethering, rolling, and firm adhesion as well as platelet secondary capture in LPS-treated mice. Rho-kinase inhibition by fasudil significantly reduced platelet tethering, rolling, and firm adhesion. Interestingly, functional blockade of Rho kinase was also able to diminish secondary platelet capture by 79%. CONCLUSIONS:: From our data, we conclude that Rho-kinase signaling plays a central role in the regulation of LPS-induced platelet-endothelial cell interactions in large veins in vivo. Thus, Rho-kinase inhibition might be useful in prevention or treatment of pathological inflammation and endotoxin-mediated hypercoagulation.},
  author       = {Slotta, Jan and Braun, Oscar and Menger, Michael and Thorlacius, Henrik},
  issn         = {1708-8267},
  language     = {eng},
  number       = {4},
  pages        = {720--725},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Investigative Medicine},
  title        = {Central Role of Rho Kinase in Lipopolysaccharide-Induced Platelet Capture on Venous Endothelium.},
  url          = {http://dx.doi.org/10.231/JIM.0b013e31816c3e81},
  volume       = {56},
  year         = {2008},
}