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.
Eppihimer
Michael J
MJ
Wyeth Research: Cardiovascular and Metabolic Diseases, Cambridge, Massachusetts, USA. mje106@psu.edu
Sushkova
Natalia
N
Lavigne
Mark C
MC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D040881:CD11a Antigen / Q000276:immunology / Q000502:physiology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002448:Cell Adhesion; D039441:Integrin alpha4 / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology*; D036904:Leukocyte Rolling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000098:blood supply; D014699:Venules / Q000166:cytology
D000911:Antibodies, Monoclonal; D040881:CD11a Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; D039441:Integrin alpha4; D015847:Interleukin-4