FK506 SUPPRESSES THE MITOGEN-INDUCED INCREASE IN LYMPHOCYTE ADHESIVENESS TO ENDOTHELIAL-CELLS, BUT DOES NOT AFFECT ENDOTHELIAL-CELL ACTIVATION IN RESPONSE TO INFLAMMATORY STIMULI

Background. In vivo studies indicate that FK506 may affect endothelial cell activation. FK506 has also been reported to affect leukocyte adh esiveness and transendothelial migration. The purpose of the present s tudy was to investigate the direct effects of FK506 on endothelial act ivation and on the increase in lymphocyte adhesiveness associated with mitogen stimulation. Methods. Using flow cytometry and enzyme-linked immunosorbent assays, we studied the effects of FR506 on expression of E-selectin and intercellular adhesion molecule 1 and on the release o f interleukin (IL) 6 and IL-8 from endothelial cells in response to in flammatory mediators, Expression of lymphocyte adhesion molecules and adhesion between lymphocytes and endothelial cells were also quantitat ed using flow cytometry. Results. Endothelial activation in response t o lipopolysaccharide, IL-1 beta, or tumor necrosis factor-alpha was fo und to be unaffected by FK506. The increase in lymphocyte adhesiveness to endothelium seen after mitogen stimulation, on the other hand, was significantly depressed by FR506. The associated changes in the expre ssion of CD11c, CD29, and CD31 were also significantly altered by FK50 6. Conclusion. In addition to its inhibitory effects on T-cell activat ion, FK506 may also interfere with processes leading to increased lymp hocyte adhesiveness. This is thus a possible additional mechanism for its beneficial effects in connection with organ rejection and autoimmu ne diseases.