Selective inhibition of adhesion molecule expression by edelfosine (ET-18-OCH3) on human umbilical vein or microvascular endothelium.
An abundance of data is accumulating that suggest that if one can block endothelial cell-leukocyte binding or inhibit cell adhesion molecules (CAM), inflammatory events can be greatly diminished. In this report, we demonstrate that an alkyl-lysophospho-lipid compound (ET-18-OCH3) can decrease adhesion molecule expression on cultured human micro- and macrovascular endothelial cell lines. ET-18 selectively decreased CAM expression; CD31 was decreased, however. Vascular CAM-1 tumor necrosis factor-alpha-induced expression was not altered. Intercellular adhesion molecule 1 expression was decreased, but endoglin expression was not affected. Thus, we have demonstrated nontoxic downmodulation of vascular CAM expression in vitro. Whether this compound will have anti-inflammatory properties needs to be clarified in animal models.
Bosse
D C
DC
Centers for Disease Control and Prevention, Biological Products Branch, Atlanta, GA 30333, USA.
Parker
J T
JT
Vogler
W R
WR
Ades
E W
EW
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002460:Cell Line; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007365:Intercellular Junctions / Q000187:drug effects; D010742:Phospholipid Ethers / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D018960:Hyaluronan Receptors; D010742:Phospholipid Ethers; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C026659:edelfosine