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Radiation-induced platelet-endothelial cell interactions are mediated by P-selectin and P-selectin glycoprotein ligand-1 in the colonic microcirculation.

Röme, Andrada LU ; Thornberg, Charlotte LU ; Santén, Stefan LU ; Mattsson, Sören LU ; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2012) In Surgery 151(4). p.606-611
Abstract
BACKGROUND: Antiplatelet reagents have been reported to protect against intestinal damage associated with abdominal radiotherapy, but the mechanisms behind radiation-induced platelet-endothelium interactions are not known. We sought to define the adhesive mechanisms that regulate radiotherapy-induced platelet-endothelial cell interactions in the colon. METHODS: All mice except the controls were exposed to abdominal radiation with a single dose of 20 Gray. Mice were pretreated with an isotype-matched control antibody or a monoclonal antibody directed against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1). Platelet and leukocyte rolling and adhesion in the colon were determined by use of inverted intravital fluorescence... (More)
BACKGROUND: Antiplatelet reagents have been reported to protect against intestinal damage associated with abdominal radiotherapy, but the mechanisms behind radiation-induced platelet-endothelium interactions are not known. We sought to define the adhesive mechanisms that regulate radiotherapy-induced platelet-endothelial cell interactions in the colon. METHODS: All mice except the controls were exposed to abdominal radiation with a single dose of 20 Gray. Mice were pretreated with an isotype-matched control antibody or a monoclonal antibody directed against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1). Platelet and leukocyte rolling and adhesion in the colon were determined by use of inverted intravital fluorescence microscopy 16 hours after radiation. Radiation-induced intestinal leakage of fluorescein isothiocyanate-conjugated dextran was examined in separate experiments. RESULTS: Immunoneutralization of P-selectin decreased radiation-provoked platelet rolling by 87% and adhesion by 63%. Moreover, inhibition of PSGL-1 decreased platelet rolling and adhesion by 77% and 83%, respectively, in animals exposed to radiation. Similarly, inhibition of P-selectin and PSGL-1 decreased radiation-induced leukocyte rolling and adhesion by more than 84% and 90%, respectively, in the colon. In contrast, inhibition of P-selectin or PSGL-1 had no impact on radiation-induced intestinal leakage. In addition, systemic depletion of platelets and leukocytes did not affect intestinal barrier dysfunction in radiated animals. CONCLUSION: This study demonstrates that radiation-provoked platelet and leukocyte accumulation are mediated in part by P-selectin and PSGL-1. Radiation-induced gut leakage, however, is independent of accumulation of platelets and leukocytes in the intestinal microvasculature. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Surgery
volume
151
issue
4
pages
606 - 611
publisher
Elsevier
external identifiers
  • wos:000301996600015
  • pmid:22153123
  • scopus:84858445090
ISSN
1532-7361
DOI
10.1016/j.surg.2011.09.045
language
English
LU publication?
yes
id
ba5bb4c0-b2cc-4686-8a96-234b3250d025 (old id 2274248)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22153123?dopt=Abstract
date added to LUP
2012-01-03 16:50:53
date last changed
2017-01-01 07:46:29
@article{ba5bb4c0-b2cc-4686-8a96-234b3250d025,
  abstract     = {BACKGROUND: Antiplatelet reagents have been reported to protect against intestinal damage associated with abdominal radiotherapy, but the mechanisms behind radiation-induced platelet-endothelium interactions are not known. We sought to define the adhesive mechanisms that regulate radiotherapy-induced platelet-endothelial cell interactions in the colon. METHODS: All mice except the controls were exposed to abdominal radiation with a single dose of 20 Gray. Mice were pretreated with an isotype-matched control antibody or a monoclonal antibody directed against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1). Platelet and leukocyte rolling and adhesion in the colon were determined by use of inverted intravital fluorescence microscopy 16 hours after radiation. Radiation-induced intestinal leakage of fluorescein isothiocyanate-conjugated dextran was examined in separate experiments. RESULTS: Immunoneutralization of P-selectin decreased radiation-provoked platelet rolling by 87% and adhesion by 63%. Moreover, inhibition of PSGL-1 decreased platelet rolling and adhesion by 77% and 83%, respectively, in animals exposed to radiation. Similarly, inhibition of P-selectin and PSGL-1 decreased radiation-induced leukocyte rolling and adhesion by more than 84% and 90%, respectively, in the colon. In contrast, inhibition of P-selectin or PSGL-1 had no impact on radiation-induced intestinal leakage. In addition, systemic depletion of platelets and leukocytes did not affect intestinal barrier dysfunction in radiated animals. CONCLUSION: This study demonstrates that radiation-provoked platelet and leukocyte accumulation are mediated in part by P-selectin and PSGL-1. Radiation-induced gut leakage, however, is independent of accumulation of platelets and leukocytes in the intestinal microvasculature.},
  author       = {Röme, Andrada and Thornberg, Charlotte and Santén, Stefan and Mattsson, Sören and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {1532-7361},
  language     = {eng},
  number       = {4},
  pages        = {606--611},
  publisher    = {Elsevier},
  series       = {Surgery},
  title        = {Radiation-induced platelet-endothelial cell interactions are mediated by P-selectin and P-selectin glycoprotein ligand-1 in the colonic microcirculation.},
  url          = {http://dx.doi.org/10.1016/j.surg.2011.09.045},
  volume       = {151},
  year         = {2012},
}