Relative contributions of alpha4 and alphaL integrins to IL-4-induced leukocyte rolling and adhesion

OBJECTIVE: To delineate the relative contributions of alpha4 and alphaL to mediate interleukin-4 (IL-4) induced leukocyte rolling, and the subsets of leukocytes that use these pathways to adhere. METHODS: Intravital microscopy was used to examine leukocytes in venules of cremaster muscles of mice receiving intrascrotal injections of IL-4. alpha4 and alphaL monoclonal antibodies (mAbs) were administrated either prior to (prophylactic) or 24 h following (therapeutic) treatment with IL-4. In addition, fluorescent microspheres coated with mAbs directed against CD4, CD8, or Gr-1 were injected into mice and the number of subset-specific adherent leukocytes was measured. RESULTS: Prophylactic inhibition of alpha4 and alphaL integrins prevented IL-4-induced leukocyte rolling flux (p< .05) and increased leukocyte rolling velocity twofold (p < .05), respectively, while blocking either integrin eliminated IL-4-induced leukocyte adhesion (p < .05). In contrast, therapeutic administration of both anti-alpha4 and anti-alphaL mAbs was necessary to completely inhibit IL-4-induced leukocyte adhesion (p < .05). Furthermore, CD8+ and Gr-1+ leukocytes utilized alpha4 and alphaL to adhere to postcapillary venules, whereas CD4+ leukocytes primarily utilized alpha4. CONCLUSIONS: Following tissue activation with IL-4, alpha4 and alphaL initiate the attachment and deceleration, respectively, of leukocytes during rolling, and are responsible for mediating the adhesion CD4+, CD8+, Gr-1+ leukocytes.