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.
Département d'Immunologie, Immunopharmacologie et Pathologie, U.A. no. 491 du CNRS, Université Louis Pasteur de Strasbourg, Illkirch, France.
A F
AF
Laurent
S
S
Dumont
P
P
Poindron
C D
CD
Muller
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