THE PHOSPHOLIPASE-A(2) REACTION LEADS TO INCREASED MONOCYTE ADHESION OF ENDOTHELIAL-CELLS VIA THE EXPRESSION OF ADHESION MOLECULES

Mononuclear cell invasion into the vascular-vessel wall is a very important initial step in the development of atherosclerotic lesions. Hypercholesterolemia leads to a marked adhesion of circulating blood monocytes to arterial endothelial cells in vivo, and minimally oxidized low-density lipoprotein enhances monocyte adhesion to endothelial cells in vitro. The activation of phospholipase A1 (PLA2) is also important in the oxidation of low-density lipoprotein by endothelial cells. In this study, we investigated the role of PLA2 activation in the adhesion of a leukemic monocyte cell line (THP-1 cells) to endothelial cells in vitro using an adhesion assay and a cell-ELISA technique. The treatment of human umbilical-cord-vein endothelial cells with PLA2 stimulators such as interleukin-1beta, tumor necrosis factor and lipopolysaccharide all increased the adhesion of THP-1 cells to endothelial cells. Exogeneous PLA2 also increased the adhesion of these cell types. The increased adhesion induced by these PLA2 stimulators, as well as PLA2 itself, was reversed by various inhibitors of the PLA2 reaction. A product of the PLA2 reaction, lysophosphatidylcholine, also increased cell adhesion. A cell-ELISA technique showed the enhanced expression of vascular-cell-adhesion-molecule 1 and intercellular-adhesion-molecule 1 to endothelial cells after treatment with PLA2 stimulators, PLA2 or lysophosphatidylcholine. These results suggest that the PLA2 reaction enhances monocyte adhesion to endothelial cells through the expression of cellular adhesion molecules.