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Role of P‐selectin in radiation‐induced intestinal inflammatory damage
Author(s) -
Mollà Meritxell,
Gironella Meritxell,
Salas Azucena,
Miquel Rosa,
PérezdelPulgar Sofia,
Conill Carles,
Engel Pablo,
Biete Albert,
Piqué Josep M.,
Panés Julián
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1009
Subject(s) - intravital microscopy , inflammation , cell adhesion molecule , selectin , adhesion , immunology , cell adhesion , p selectin , irradiation , chemistry , e selectin , biology , microbiology and biotechnology , medicine , microcirculation , platelet , physics , platelet activation , organic chemistry , nuclear physics
The aims of our study were to characterize the dose‐ and time‐dependent changes in endothelial P‐selectin expression and the role of this adhesion molecule as a mediator of radiation‐induced inflammation. For that purpose, endothelial P‐selectin expression was measured by the radiolabeled antibody technique in control and irradiated mice at 2, 6, and 24 hr following abdominal irradiation with 4 or 10 Gy; leukocyte endothelial cell interactions were assessed using intravital microscopy in intestinal venules following irradiation at the aforementioned doses and times in C57BL/6 and P‐selectin‐deficient mice. In wild‐type mice, radiation induced a time‐ and dose‐dependent up‐regulation of P‐selectin and a significant increase in the flux of rolling leukocytes 2 hr after irradiation. Irradiation induced a significant increase in leukocyte adhesion that was dose‐dependent. Following irradiation, P‐selectin‐deficient mice did not show any increase in leukocyte rolling but did demonstrate a response in leukocyte adhesion similar to that of the wild‐type mice. Radiation‐induced dose‐dependent histological inflammatory damage that did not differ between P‐selectin‐deficient and wild‐type mice. We conclude that P‐selectin is up‐regulated following irradiation and is a key molecular determinant of leukocyte rolling but not leukocyte adhesion in this inflammatory condition. Therefore, isolated neutralization of this adhesion molecule is not an effective means for preventing radiation‐induced inflammation. © 2001 Wiley‐Liss, Inc.