MONONUCLEAR LEUKOCYTES EXPOSED TO OXIDIZED LOW-DENSITY-LIPOPROTEIN SECRETE A FACTOR THAT STIMULATES ENDOTHELIAL-CELLS TO EXPRESS ADHESION MOLECULES

In animals fed a hypercholesterolemic diet, development of artheroscle rosis is preceded by attachment of mononuclear leukocytes to the arter ial endothelium. Early lesions begin to develop as monocytes migrate i nto the intima and ingest lipids. A major part of these lipids is beli eved to be derived from oxidatively modified low density lipoprotein ( LDL). In the present study we demonstrate that human mononuclear leuko cytes exposed to low concentrations of copper-oxidized LDL secrete one or several factors that stimulate the expression of intercellular adh esion molecule-1 (ICAM-1, CD54), vascular cell adhesion molecule (VCAM -1) and endothelial selectin (E-selectin-1, ELAM-1), whereas native LD L was found to be without effect. Exposure of endothelial cells to non -conditioned medium containing oxidized LDL did not influence the expr ession of adhesion molecules. Incubation of endothelial cells with con ditioned medium from mononuclear cells grown in the presence of oxidiz ed LDL also resulted in a three-fold increase in the binding of monocy toid U937 cells. The present findings suggest that mononuclear leukocy tes exposed to oxidatively modified LDL in early atherosclerotic lesio ns may stimulate the recruitment of other leukocytes by secreting cyto kines which induce the expression of adhesion molecules on the endothe lium.