FK506 (tacrolimus) inhibits extravasation of lymphoid cells by abrogating VLA-4/VCAM-1 mediated transendothelial migration.
Extravasation is a critical process for the physiological lymphocyte traffic as well as the hematogenous spread of malignant hemopoietic cells. Here we report that abrogation of calcineurin activity leads to in vitro transendothelial migration and in vivo infiltration of human lymphoma Nalm-6 cells, which are associated with the abrogation of the VLA-4/VCAM-1 mediated pathway. Rapamycin, which can antagonize FK506 but not CsA to inhibit calcineurin, abrogates FK-506 mediated but not CsA mediated inhibition of in vitro transendothelial migration. FK506 may exert its potent immunosuppressive action partly by inhibiting VLA-4/VCAM-1 mediated transendothelial migration or insinuation of lymphoid cells to tissues.
Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Japan.
S
S
Tsuzuki
N
N
Toyama-Sorimachi
F
F
Kitamura
Y
Y
Tobita
M
M
Miyasaka
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D001854:Bone Marrow Cells; D019703:Calcineurin / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects*; D002490:Central Nervous System / Q000166:cytology; D004727:Endothelium / Q000166:cytology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D016393:Lymphoma, B-Cell; D051379:Mice; D016513:Mice, SCID; D011090:Polyenes / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D020123:Sirolimus; D013154:Spleen / Q000166:cytology; D016559:Tacrolimus / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
D007166:Immunosuppressive Agents; D039041:Integrin alpha4beta1; D016023:Integrins; D011090:Polyenes; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D019703:Calcineurin; D020123:Sirolimus; D016559:Tacrolimus