DOWN-REGULATION OF THE SELECTIN LIGAND-PRODUCING FUCOSYL-TRANSFERASESFUC-TIV AND FUC-TVII DURING FOAM CELL-FORMATION IN MONOCYTE-DERIVED MACROPHAGES

Identification of genes expressed during foam cell formation is import ant for understanding the molecular basis of atherosclerosis. We used polymerase chain reaction (PCR)-based differential display to isolate differentially expressed cDNA species in foam cells induced by incubat ion of human monocyte-derived macrophages in the presence of acetylate d or oxidized LDL. This led to identification of a 306-bp cDNA with 10 0% homology to type IV fucosyltransferase (Fuc-TIV), which was downreg ulated by factors of 20 and 3 in acetylated LDL- and oxidized LDL-load ed macrophages, respectively. This enzyme is sufficient for the expres sion of Lewis X and sialyl Lewis X, carbohydrate adhesion molecules th at bind to receptors of the selectin family. Expression of a second fu cosyltransferase (Fuc-TVII) that synthesizes sialyl Lewis X but not Le wis X was shown by quantitative reverse transcription-PCR to also be r educed, by 40% and 20% in acetylated LDL- and oxidized LDL-loaded macr ophages, respectively. alpha-(1,3) Fucosyltransferase enzyme activity was reduced in lysates from both acetylated LDL-and oxidized LDL-loade d cells. Analysis by flow cytometry showed reduced expression of the C D15 (corresponding to Lewis X) and CD15s (sialyl Lewis X) antigens on the surface of cells loaded with either acetylated or oxidized LDL. Tr ansformation of macrophages into foam cells results in reduced express ion of selectin-binding ligands on the surface of such cells.