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Critical Role of P-Selectin and Lymphocyte Function Antigen-1 in Radiation-Induced Leukocyte-Endothelial Cell Interactions in the Colon

  • Original Contribution
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Diseases of the Colon & Rectum

Abstract

Purpose

Radiation therapy is frequently used in treating different types of tumors, although associated with serious side effects, such as fibrosis and complicated diarrhea. This study was designed to define the adhesive mechanisms behind radiotherapy-induced leukocyte recruitment in the colon.

Methods

All mice, except control animals, were radiated with a single dose of 20 Gy. Mice were pretreated with an isotype-matched control antibody or a monoclonal antibody directed against P-selectin. In separate experiments, lymphocyte function antigen-1–deficient animals were used. Leukocyte rolling and firm adhesion were determined by use of inverted intravital fluorescence microscopy 16 hours after radiation.

Results

It was found that immunoneutralization of P-selectin reduced leukocyte rolling by 83 percent and adhesion by 87 percent in radiated mice. Moreover, radiation-induced leukocyte adhesion in LFA-1-deficient mice was decreased by 94 percent compared with wild-type animals.

Conclusions

This study demonstrates that leukocyte rolling is mediated by P-selectin and that firm leukocyte adhesion is supported by lymphocyte function antigen-1 in radiation-induced enteritis. Moreover, P-selectin-dependent leukocyte rolling is a precondition for subsequent leukocyte adhesion in radiation-induced intestinal injury. Thus, targeting P-selectin and/or lymphocyte function antigen-1 may protect against pathologic inflammation in the colon induced by radiotherapy.

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Authors and Affiliations

  1. Department of Surgery, Malmö University Hospital, Lund University, SE 205 02, Malmö, Sweden

    Andrada Mihaescu M.D., Yusheng Wang Ph.D., Bengt Jeppsson M.D., Ph.D. & Henrik Thorlacius M.D., Ph.D.

  2. Department of Radiation Physics, Malmö University Hospital, Lund University, Malmö, Sweden

    Charlotte Thornberg Ph.D. & Sören Mattsson Ph.D.

Authors
  1. Andrada Mihaescu M.D.
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  2. Charlotte Thornberg Ph.D.
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  3. Sören Mattsson Ph.D.
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  4. Yusheng Wang Ph.D.
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  5. Bengt Jeppsson M.D., Ph.D.
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  6. Henrik Thorlacius M.D., Ph.D.
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Corresponding author

Correspondence to Henrik Thorlacius M.D., Ph.D..

Additional information

Supported by Swedish Medical Research Council (2003–4661, 2006–4889), Crafoordska stiftelsen, Einar och Inga Nilssons stiftelse, Greta och Johan Kocks stiftelser, Fröken Agnes Nilssons stiftelse, Magnus Bergvalls stiftelse, Mossfelts stiftelse, Nanna Svartz stiftelse, Ruth och Richard Julins stiftelse, Dir. A. Påhlsson’s Foundation, Swedish Cancer Foundation, Malmö University Hospital Cancer Foundation, Lundgren’s Foundation, Gunnar Nilsson’s Foundation and Apotekaren Hedberg’s Fond, Malmö University Hospital and Lund University.

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Mihaescu, A., Thornberg, C., Mattsson, S. et al. Critical Role of P-Selectin and Lymphocyte Function Antigen-1 in Radiation-Induced Leukocyte-Endothelial Cell Interactions in the Colon. Dis Colon Rectum 50, 2194–2202 (2007). https://doi.org/10.1007/s10350-007-9065-7

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  • DOI: https://doi.org/10.1007/s10350-007-9065-7

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