Mycophenolic acid suppresses protein N-linked glycosylation in human monocytes and their adhesion to endothelial cells and to some substrates.
Mycophenolic acid (MPA) is the active part of the corresponding morpholinoethyl ester pro-drug Mycophenolate Mofetil. MPA, an inhibitor of IMP dehydrogenase, depletes GTP and thereby suppresses transfer of mannose and fucose to proteins. Treatment of human monocytes with a clinically attainable concentration of MPA (10 microM) decreases their attachment to endothelial cells and to laminin, but not to type I collagen or fibronectin. Our results not only elucidate a major role of mannose/fucose residues in homing of monocytes on activated endothelium but also explain in part the beneficial effects of MPA in rheumatoid arthritis and organ graft rejection.
Laurent
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AF
Département d'Immunologie, Immunopharmacologie et Pathologie, U.A. no. 491 du CNRS, Université Louis Pasteur de Strasbourg, Illkirch, France.
Dumont
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S
Poindron
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Muller
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D000954:Antigens, Surface / Q000032:analysis; D002236:Carbohydrate Conformation; D002448:Cell Adhesion / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D005643:Fucose / Q000737:chemistry; D006023:Glycoproteins / Q000096:biosynthesis; D006031:Glycosylation; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007797:Laminin / Q000378:metabolism; D008358:Mannose / Q000737:chemistry; D008361:Mannosidases / Q000494:pharmacology; D009000:Monocytes / Q000737:chemistry* / Q000166:cytology* / Q000187:drug effects; D009173:Mycophenolic Acid / Q000494:pharmacology*; D010587:Phagocytosis; D043323:alpha-Mannosidase
D000954:Antigens, Surface; D016207:Cytokines; D004791:Enzyme Inhibitors; D005353:Fibronectins; D006023:Glycoproteins; D007797:Laminin; D005643:Fucose; D003094:Collagen; D007168:IMP Dehydrogenase; D008361:Mannosidases; D043323:alpha-Mannosidase; D009173:Mycophenolic Acid; D008358:Mannose