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(Journal of Leukocyte Biology. 2003;73:65-73.)
© 2003 by Society for Leukocyte Biology

P-selectin mediates IL-13-induced eosinophil transmigration but not eotaxin generation in vivo: a comparative study with IL-4-elicited responses

Karen Y. Larbi^*, John P. Dangerfield^*, Fiona J. Culley, Diane Marshall^*, Dorian O. Haskard^*, Peter J. Jose, Timothy J. Williams and Sussan Nourshargh^*

^* BHF Cardiovascular Medicine Unit, National Heart & Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, United Kingdom; and
Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, United Kingdom

Correspondence: Dr. Karen Larbi, BHF Cardiovascular Medicine Unit, National Heart and Lung Institute, Faculty of Medicine, Imperial College, Hammersmith Hospital, DuCane Road, London W12 0NN, U.K. E-mail: k.larbi{at}ic.ac.uk

The study investigated the role of P-selectin in the responses of eosinophil transmigration and eotaxin generation in vivo elicited by interleukin (IL)-13, as compared with IL-4. Two murine models of leukocyte transmigration were used, migration into cytokine-stimulated peritoneal cavities and through stimulated cremasteric venules, as observed by intravital microscopy. In mice lacking P-selectin, eosinophil infiltration elicited by the cytokines in the peritonitis model was totally inhibited. In the cremaster muscle, however, although spontaneous leukocyte-rolling flux and stimulated leukocyte firm adhesion were inhibited by 97% and 48%, respectively, stimulated transmigration was unaffected. However, IL-13-induced leukocyte transmigration was totally blocked in P-selectin-deficient mice treated with an anti-₄ integrin monoclonal antibody (mAb; PS/2). In comparison, treatment of wild-type mice with the anti-₄ integrin mAb resulted in only partial suppression of IL-13-induced leukocyte transmigration. Significant levels of eotaxin were detected in response to IL-13/IL-4 in both tissues in P-selectin-deficient animals. In conclusion, the regulatory role of P-selectin in leukocyte transmigration elicited by IL-13 appears to be tissue-specific, a phenomenon that is independent of the ability of the cytokine to stimulate eotaxin generation.

Key Words: cytokines • chemokines • adhesion molecules • eosinophils • in vivo animal models

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