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 adhesiveness and transendothelial migration. The purpose of the present study was to investigate the direct effects of FK506 on endothelial activation 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 FK506 on expression of E-selectin and intercellular adhesion molecule 1 and on the release of interleukin (IL) 6 and IL-8 from endothelial cells in response to inflammatory mediators. Expression of lymphocyte adhesion molecules and adhesion between lymphocytes and endothelial cells were also quantitated using flow cytometry.


RESULTS
Endothelial activation in response to lipopolysaccharide, IL-1beta, or tumor necrosis factor-alpha was found to be unaffected by FK506. The increase in lymphocyte adhesiveness to endothelium seen after mitogen stimulation, on the other hand, was significantly depressed by FK506. The associated changes in the expression of CD11c, CD29, and CD31 were also significantly altered by FK506.


CONCLUSIONS
In addition to its inhibitory effects on T-cell activation, FK506 may also interfere with processes leading to increased lymphocyte adhesiveness. This is thus a possible additional mechanism for its beneficial effects in connection with organ rejection and autoimmune diseases.
Karlsson
H
H
Department of Biochemistry, Stockholm University, Sweden. welchlink.welch.jhu.edu.
Nässberger
L
L
D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication; D002469:Cell Separation / Q000379:methods; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology*; D008934:Mitogens / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology; D016559:Tacrolimus / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015850:Interleukin-6; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D016559:Tacrolimus