Radiation-induced platelet-endothelial cell interactions are mediated by P-selectin and P-selectin glycoprotein ligand-1 in the colonic microcirculation.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2274248
- author
- Röme, Andrada LU ; Thornberg, Charlotte LU ; Santén, Stefan LU ; Mattsson, Sören LU ; Jeppsson, Bengt LU and Thorlacius, Henrik LU
- organization
- publishing date
- 2012
- 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
- 2016-04-04 09:18:30
- date last changed
- 2022-01-29 17:16:55
@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}},
doi = {{10.1016/j.surg.2011.09.045}},
volume = {{151}},
year = {{2012}},
}