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 t raffic as well as the hematogenous spread of malignant hemopoietic cel ls. Here me report that abrogation of calcineurin activity leads to in vitro transendothelial migration and in vivo infiltration of human ly mphoma Nalm-6 cells, which are associated with the abrogation of the V LA-4/VCAM-1 mediated pathway. Rapamycin, which can antagonize FK506 bu t not CsA to inhibit calcineurin, abrogates FK-506 mediated but not Cs A mediated inhibition of in vitro transendothelial migration. FK506 ma y exert its potent immunosuppressive action partly by inhibiting VLA-4 /VCAM-1 mediated transendothelial migration or insinuation of lymphoid cells to tissues. (C) 1998 Federation of European Biochemical Societi es.