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

Röme, Andrada LU ; Thornberg, Charlotte LU ; Mattsson, Sören LU ; Wang, Yusheng LU ; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2007) In Diseases of the Colon & Rectum 50(12). p.2194-2202
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diseases of the Colon & Rectum
volume
50
issue
12
pages
2194 - 2202
publisher
Springer
external identifiers
  • wos:000251641700027
  • scopus:37249027788
ISSN
0012-3706
DOI
10.1007/s10350-007-9065-7
language
English
LU publication?
yes
id
48da384a-a98c-4c81-88e4-d1bc156c9e46 (old id 607851)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17851717&dopt=Abstract
date added to LUP
2008-08-08 13:33:56
date last changed
2017-02-05 03:39:32
@article{48da384a-a98c-4c81-88e4-d1bc156c9e46,
  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.<br/><br>
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.<br/><br>
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.<br/><br>
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.},
  author       = {Röme, Andrada and Thornberg, Charlotte and Mattsson, Sören and Wang, Yusheng and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {0012-3706},
  language     = {eng},
  number       = {12},
  pages        = {2194--2202},
  publisher    = {Springer},
  series       = {Diseases of the Colon & Rectum},
  title        = {Critical Role of P-Selectin and Lymphocyte Function Antigen-1 in Radiation-Induced Leukocyte-Endothelial Cell Interactions in the Colon.},
  url          = {http://dx.doi.org/10.1007/s10350-007-9065-7},
  volume       = {50},
  year         = {2007},
}