1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) is a synthetic inhibitor toward glucosyl transferase. Here, we showed the functional role of sphingolipids on CD54 expression of endothelial cells (ECs) by the use of PDMP. CD54 mRNA expression in human umbilical vein endothelial cells (HUVECs) was not changed by PDMP; however, PDMP treatment significantly enhanced the expression of membrane-bound CD54 (mCD54) on HUVECs. In contrast, the amount of soluble form of CD54 (sCD54) in the culture supernatants of HUVECs was diminished by PDMP. Similar results were obtained when HUVECs were incubated with metalloproteinase inhibitor, KB-R8301, or in the presence of C2-ceramide. The above effect of PDMP, KB-R8301, and C2-ceramide in HUVECs was commonly found in unstimulated, TNF-alpha-stimulated, and IL-1beta-stimulated HUVECs. These data provide the possibility that the shedding of mCD54 into sCD54 by metalloproteinase-like enzyme is inhibited by PDMP, in which PDMP-induced accumulation of ceramide may act as a second messenger. (C) 2002 Elsevier Science (USA). All rights reserved.