Effects of desferrioxamine on human cytomegalovirus replication and expression of HLA antigens and adhesion molecules in human vascular endothelial cells.
Desferrioxamine (DFO), commonly used in therapy as a chelator of ferric ion in disorders of iron overload, is a potent inhibitor of human cytomegalovirus (HCMV) replication in cultured fibroblast cells. Moreover, DFO has immunomodulatory activity both in vitro and in vivo. We studied DFO effects on HCMV replication in cultured human endothelial cells and on the expression of several cell surface molecules, which mediate interactions of endothelial cells with other cell types in the immune system. The concentrations of DFO required for 50% reduction in the number of endothelial cells expressing HCMV late antigen, ranged for several HCMV strains from 5.2 to 8.8 microM. DFO concentrations ranging from 5 to 40 microM inhibited cellular DNA synthesis in a dose-dependent manner without any significant effects on the cell viability. DFO at 10 microM concentration suppressed expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1), while it had no significant effect on the expression of vascular cell adhesion molecule-1 (VCAM-1). Expression of HLA class I and class II was not influenced by DFO treatment. The results showed that DFO is both effective in inhibition of HCMV replication and expression of ICAM-1 and ELAM-1 in endothelial cells, a combination that warrants attention to its potential use to prevent HCMV-induced allograft rejection in transplant recipients.
Cinatl
J
J
Institut für Medizinische Virologie, Zentrum der Hygiene, Frankfurt, Germany.
Scholz
M
M
Weber
B
B
Cinatl
J
J
Rabenau
H
H
Markus
B H
BH
Encke
A
A
Doerr
H W
HW
D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D003676:Deferoxamine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D005347:Fibroblasts / Q000821:virology; D006680:HLA Antigens / Q000096:biosynthesis*; D006801:Humans; D014779:Virus Replication / Q000187:drug effects
D015815:Cell Adhesion Molecules; D006680:HLA Antigens; D004247:DNA; D003676:Deferoxamine