Quantification of the influence of mycophenolic acid on the release of endothelial adhesion molecules.
BACKGROUND
Mycophenolic acid selectively inhibits inosine 5'-monophosphate dehydrogenase leading to a shortage of guanosine nucleotides. Since GTP is required for the synthesis of glycoproteins, this immunosuppressive drug also influences the production of several cell adhesion molecules.


METHODS
Soluble endothelial cell adhesion molecules released into cell culture supernatants after an incubation period of 16 h are assessed via a standard ELISA procedure applying test kits for E-selectin, VCAM-1 and ICAM-1.


RESULTS
Treatment with TNF-alpha leads to the induction of E-selectin and causes a significant increase in VCAM-1 and ICAM-1 content in the supernatant in relation to the level of unstimulated cells. Due to the inhibitory effects of MPA-applied either alone or in combination with cyclosporin A and prednisolone-sE-selectin is significantly reduced and sVCAM-1 is slightly but not significantly decreased, whereas sICAM-1 levels remain unchanged.


CONCLUSIONS
We demonstrate that the influence of MPA on endothelial cell adhesion molecules can readily be determined via ELISA. The results indicate that the immunosuppression by MPA is also achieved by slightly reducing the expression and consequent release of E-selectin, a pivotal molecule in the first step of leucocyte-endothelial interactions.
Raab
Markus
M
Institute of Laboratory Diagnostics and Ludwig Boltzmann Institute for Cardiothoracic Research, Kaiser-Franz-Josef Hospital, Kundratstrasse 3, A-1100 Vienna, Austria. other_mr@yahoo.de
Daxecker
Heide
H
Pavlovic
Vladimir
V
Griesmacher
Andrea
A
Mueller
Mathias M
MM
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009173:Mycophenolic Acid / Q000494:pharmacology*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009173:Mycophenolic Acid