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Radiation-induced p...
Radiation-induced platelet-endothelial cell interactions are mediated by P-selectin and P-selectin glycoprotein ligand-1 in the colonic microcirculation.
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- Röme, Andrada (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Thornberg, Charlotte (författare)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Malmö,Forskargrupper vid Lunds universitet,Medical Radiation Physics, Malmö,Lund University Research Groups
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- Santén, Stefan (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Mattsson, Sören (författare)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Malmö,Forskargrupper vid Lunds universitet,Medical Radiation Physics, Malmö,Lund University Research Groups
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- Jeppsson, Bengt (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Thorlacius, Henrik (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2012
- 2012
- Engelska.
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Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 151:4, s. 606-611
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
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