PMID- 10353469
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20161018
IS  - 1434-6621 (Print)
IS  - 1434-6621 (Linking)
VI  - 37
IP  - 3
DP  - 1999 Mar
TI  - Alterations of endothelial nucleotide levels by mycophenolic acid result in 
      changes of membrane glycosylation and E-selectin expression.
PG  - 259-64
AB  - The effect of the inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH), 
      mycophenolic acid, on intracellular nucleotides and the synthesis of cellular 
      glycoproteins was evaluated in human umbilical vein endothelial cells. A 
      clinically attainable concentration (10 micromol/l) of mycophenolic acid 
      decreased guanosine-5'-triphosphate (GTP) levels significantly and led to a 
      strong elevation of uridine-5'-triphosphate (UTP), whereas intracellular 
      adenosine-5'-triphosphate (ATP) pools remained unaffected. The staining of the 
      endothelial cell membranes with lectins specific for fucose and mannose (Ulex 
      europaeus- and Galanthus nivalis agglutinin, respectively) was reduced, 
      reflecting an inhibition of fucose and mannose incorporation into endothelial 
      glycoproteins. The surface expression of E-selectin, an important determinant for 
      leuko-endothelial interactions decreased significantly. Guanine and guanosine 
      prevented the actions of mycophenolic acid and reversed the drug-induced decrease 
      in GTP and its associated effects. The findings that mycophenolic acid produces 
      alterations in the formation of glycoproteins and in the membrane architecture 
      are indicative of metabolic lesions induced by an agent that depresses guanine 
      nucleotide synthesis through inhibition of IMPDH. The pronounced reduction of 
      E-selectin surface expression on endothelial cells accompanied by changes of 
      endothelial cell fucosylation, a prerequisite for the contact with lymphocytic 
      L-selectin, indicates an inhibitory effect of mycophenolic acid in the rolling 
      phase of leukocyte recruitment and strongly implies a new and additional 
      immunosuppressive mechanism of this agent.
FAU - Bertalanffy, P
AU  - Bertalanffy P
AD  - Department of Cardiothoracic Surgery, University of Vienna, Austria.
FAU - Dubsky, P
AU  - Dubsky P
FAU - Wolner, E
AU  - Wolner E
FAU - Weigel, G
AU  - Weigel G
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Clin Chem Lab Med
JT  - Clinical chemistry and laboratory medicine
JID - 9806306
RN  - 0 (E-Selectin)
RN  - 0 (Nucleotides)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - UT0S826Z60 (Uridine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Cell Membrane/metabolism
MH  - Cells, Cultured
MH  - E-Selectin/*metabolism
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Flow Cytometry
MH  - Galanthus
MH  - Glycosylation
MH  - Guanosine Triphosphate/metabolism
MH  - Humans
MH  - Mycophenolic Acid/*pharmacology
MH  - Nucleotides/*metabolism
MH  - Uridine Triphosphate/metabolism
EDAT- 1999/06/03 00:00
MHDA- 1999/06/03 00:01
CRDT- 1999/06/03 00:00
PHST- 1999/06/03 00:00 [pubmed]
PHST- 1999/06/03 00:01 [medline]
PHST- 1999/06/03 00:00 [entrez]
AID - 10.1515/CCLM.1999.045 [doi]
PST - ppublish
SO  - Clin Chem Lab Med. 1999 Mar;37(3):259-64. doi: 10.1515/CCLM.1999.045.