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Primary and secondary capture of platelets onto inflamed femoral artery endothelium is dependent on P-selectin and PSGL-1.

Braun, Oscar LU ; Slotta, Jan E; Menger, Michael D; Erlinge, David LU and Thorlacius, Henrik LU (2008) In European Journal of Pharmacology 592. p.128-132
Abstract
Platelets constitute a key role in vascular injuries, however, the detailed mechanisms behind platelet-endothelial cell and platelet-leukocyte interactions in the femoral artery are not yet fully elucidated. We used intravital fluorescence microscopy of the femoral artery in C57BL/6 mice to study primary and secondary capture of platelets onto endothelial cells as well as onto adherent platelets and leukocytes in vivo. By use of monoclonal antibodies, the role of P-selectin and P-selectin glycoprotein ligand 1 (PSGL-1) in these adhesive interactions in mice exposed to endotoxin was determined. Intravenous injection of endotoxin significantly increased gene expression of P-selectin as well as platelet tethering, rolling and adhesion in the... (More)
Platelets constitute a key role in vascular injuries, however, the detailed mechanisms behind platelet-endothelial cell and platelet-leukocyte interactions in the femoral artery are not yet fully elucidated. We used intravital fluorescence microscopy of the femoral artery in C57BL/6 mice to study primary and secondary capture of platelets onto endothelial cells as well as onto adherent platelets and leukocytes in vivo. By use of monoclonal antibodies, the role of P-selectin and P-selectin glycoprotein ligand 1 (PSGL-1) in these adhesive interactions in mice exposed to endotoxin was determined. Intravenous injection of endotoxin significantly increased gene expression of P-selectin as well as platelet tethering, rolling and adhesion in the femoral artery. Pretreatment with the anti-PSGL-1 antibody decreased platelet tethering by 85%, platelet rolling by 88% and platelet adhesion by 96%. Immunoneutralization of P-selectin reduced platelet tethering by 91%, platelet rolling by 98%, and platelet adhesion by 97%. In addition, inhibition of P-selectin and PSGL-1 completely abolished secondary capture of platelets onto adherent platelets and leukocytes. Our data show that P-selectin and PSGL-1 mediate early interactions between platelets and other cells, including endothelial cells and leukocytes, in inflamed arteries. These novel results suggest that interference with P-selectin and PSGL-1 may be a useful target in strategies aiming to protect the vascular wall during arterial inflammation. (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
European Journal of Pharmacology
volume
592
pages
128 - 132
publisher
Elsevier
external identifiers
  • wos:000259434400021
  • pmid:18644365
  • scopus:49749144880
ISSN
1879-0712
DOI
10.1016/j.ejphar.2008.06.102
language
English
LU publication?
yes
id
350aaee9-b7cc-41c6-9b7a-2141709b9dd6 (old id 1180955)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18644365?dopt=Abstract
date added to LUP
2008-08-11 11:27:15
date last changed
2017-01-01 07:35:00
@article{350aaee9-b7cc-41c6-9b7a-2141709b9dd6,
  abstract     = {Platelets constitute a key role in vascular injuries, however, the detailed mechanisms behind platelet-endothelial cell and platelet-leukocyte interactions in the femoral artery are not yet fully elucidated. We used intravital fluorescence microscopy of the femoral artery in C57BL/6 mice to study primary and secondary capture of platelets onto endothelial cells as well as onto adherent platelets and leukocytes in vivo. By use of monoclonal antibodies, the role of P-selectin and P-selectin glycoprotein ligand 1 (PSGL-1) in these adhesive interactions in mice exposed to endotoxin was determined. Intravenous injection of endotoxin significantly increased gene expression of P-selectin as well as platelet tethering, rolling and adhesion in the femoral artery. Pretreatment with the anti-PSGL-1 antibody decreased platelet tethering by 85%, platelet rolling by 88% and platelet adhesion by 96%. Immunoneutralization of P-selectin reduced platelet tethering by 91%, platelet rolling by 98%, and platelet adhesion by 97%. In addition, inhibition of P-selectin and PSGL-1 completely abolished secondary capture of platelets onto adherent platelets and leukocytes. Our data show that P-selectin and PSGL-1 mediate early interactions between platelets and other cells, including endothelial cells and leukocytes, in inflamed arteries. These novel results suggest that interference with P-selectin and PSGL-1 may be a useful target in strategies aiming to protect the vascular wall during arterial inflammation.},
  author       = {Braun, Oscar and Slotta, Jan E and Menger, Michael D and Erlinge, David and Thorlacius, Henrik},
  issn         = {1879-0712},
  language     = {eng},
  pages        = {128--132},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Primary and secondary capture of platelets onto inflamed femoral artery endothelium is dependent on P-selectin and PSGL-1.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2008.06.102},
  volume       = {592},
  year         = {2008},
}