P-selectin mediates IL-13-induced eosinophil transmigration but not eotaxin generation in vivo: a comparative study with IL-4-elicited responses.
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 approximately 97% and approximately 48%, respectively, stimulated transmigration was unaffected. However, IL-13-induced leukocyte transmigration was totally blocked in P-selectin-deficient mice treated with an anti-alpha(4) integrin monoclonal antibody (mAb; PS/2). In comparison, treatment of wild-type mice with the anti-alpha(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.
Larbi
Karen Y
KY
BHF Cardiovascular Medicine Unit, National Heart & Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, UK. k.larbi@ic.ac.uk
Dangerfield
John P
JP
Culley
Fiona J
FJ
Marshall
Diane
D
Haskard
Dorian O
DO
Jose
Peter J
PJ
Williams
Timothy J
TJ
Nourshargh
Sussan
S
D000818:Animals; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D004804:Eosinophils / Q000166:cytology*; D039441:Integrin alpha4 / Q000502:physiology; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D036904:Leukocyte Rolling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000098:blood supply; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D014699:Venules / Q000166:cytology
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D018793:Interleukin-13; D019007:P-Selectin; D039441:Integrin alpha4; D015847:Interleukin-4