Transendothelial migration of human basophils.
During allergic reactions, basophils migrate from the blood compartment to inflammatory sites, where they act as effector cells in concert with eosinophils. Because transendothelial migration (TEM) represents an essential step for extravasation of cells, for the first time we have studied basophil TEM using HUVEC. Treatment of HUVEC with IL-1beta significantly enhanced basophil TEM, which was further potentiated by the presence of a CCR3-specific ligand, eotaxin/CCL11. In addition to CCR3 ligands, MCP-1/CCL2 was also active on basophil TEM. Although stromal cell-derived factor-1/CXCL12, a CXCR4 ligand, failed to induce TEM in freshly isolated basophils, it caused strong TEM in 24-h cultured cells. IL-3 enhanced basophil TEM by increasing the chemokinetic response. Spontaneous TEM across activated HUVEC was inhibited by treatment of cells with anti-CD18 mAb, but not with anti-CD29 mAb, and also by treatment of HUVEC with anti-ICAM-1 mAb. Anti-VCAM-1 mAb alone failed to inhibit TEM, but showed an additive inhibitory effect in combination with anti-ICAM-1 mAb. In contrast, eotaxin- and IL-3-mediated TEM was significantly inhibited by anti-CD29 mAb as well as anti-CD18 mAb. These results indicate that beta2 integrins play the primary role in basophil TEM, but beta1 integrins are also involved, especially in TEM of cytokine/chemokine-stimulated basophils. In conclusion, the regulatory profile of basophil TEM is very similar to that reported for eosinophils. Our results thus support the previous argument for a close relationship between basophils and eosinophils and suggest that the in vivo kinetics of these two cell types are similar.
Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Hongo, Bunkyo-ku, Japan. iikura-tky@umin.ac.jp
Motoyasu
M
Iikura
Motohiro
M
Ebisawa
Masao
M
Yamaguchi
Hiroshi
H
Tachimoto
Ken
K
Ohta
Kazuhiko
K
Yamamoto
Koichi
K
Hirai
D000818:Animals; D001491:Basophils / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018925:Chemokines / Q000494:pharmacology; D019742:Chemokines, CC / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
C515456:CCL11 protein, human; D018821:CD18 Antigens; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018925:Chemokines; D019742:Chemokines, CC; D019012:Integrin beta1; D007375:Interleukin-1; D007377:Interleukin-3; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1