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

Abstract

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-α4 integrin monoclonal antibody (mAb; PS/2). In comparison, treatment of wild-type mice with the anti-α4 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.