FK506 inhibits human lymphocyte migration and the production of lymphocyte chemotactic factors in liver allograft recipients.
The macroglide immunosuppressant FK506 is effective at preventing and reversing hepatic allograft rejection. The establishment of graft rejection is dependent upon an influx of lymphocytes from the circulation into the graft in response to locally secreted chemotactic factors. Thus, inhibition of lymphocyte migration might be an additional mode of action of FK506 that could block lymphocyte recruitment to rejecting liver allografts. In the present study, we provide evidence to support this hypothesis because we have demonstrated, using in vitro migration assays, that FK506 can inhibit the migration of lymphocytes, including CD4+ and CD8+ T-cells, to structurally diverse chemotactic factors that are present during human liver allograft rejection. In addition, FK506 acts on lymphocytes in patients with graft rejection to inhibit migration and to block the secretion of chemotactic factors in vitro. Thus, FK506 might reverse established graft rejection by inhibiting lymphocyte recruitment to the graft in vivo.
Adams
D H
DH
The Liver Unit Laboratories, Queen Elizabeth Hospital, Edgbaston, Birmingham, England.
Liu
Q
Q
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D016022:Case-Control Studies; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000494:pharmacology; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002630:Chemotactic Factors; D007166:Immunosuppressive Agents; D013755:Tetradecanoylphorbol Acetate; D016559:Tacrolimus