Relative Contributions of α₄ and α_L Integrins to IL-4-Induced Leukocyte Rolling and Adhesion

Abstract

Objective: To delineate the relative contributions of α₄ and α _L 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. α₄ and α_L 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 α₄ and α_L 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-α₄ and anti-α_L mAbs was necessary to completely inhibit IL-4-induced leukocyte adhesion (p <. 05). Furthermore, CD8⁺ and Gr-1⁺ leukocytes utilized α₄ and α_L to adhere to postcapillary venules, whereas CD4⁺ leukocytes primarily utilized α₄.

Conclusions: Following tissue activation with IL-4, α₄ and α_L initiate the attachment and deceleration, respectively, of leukocytes during rolling, and are responsible for mediating the adhesion CD4⁺, CD8⁺, Gr-1⁺ leukocytes.

KEY WORDS:

• adhesion
• endothelium
• integrins
• leukocyte rolling
• LFA-1
• VLA-4