Monocytic cell adhesion to endothelial cells stimulated by oxidized low density lipoprotein is mediated by distinct...

Treatment of human umbilical vein endothelial cells (HUVEC) with oxidized low density lipoprotein (ox-LDL, 100 microg/ml) for 24 h increased adhesion of human monocytic Mono Mac 6 cells from 4.8 +/- 0.9% to 17.6 +/- 2.5% (P < 0.001). The effect was dose dependent and first evident at 10 microg/ml ox-LDL. In contrast, adhesion of U937 cells was not significantly increased. Mac-1 (CD11b/CD18), a monocytic counter-receptor for intercellular adhesion molecule-1 (ICAM-1), that also binds to heparin, is present on Mono Mac 6 but not on U937 cells, and may thus explain these differences in adhesion. Consistently, ox-LDL induced a 2-fold upregulation of ICAM-1 surface expression on HUVEC. The presence of maltose-1-phosphate or heparin but not monoclonal antibodies (mAbs) to ICAM-1 reduced adhesion of Mono Mac 6 cells to untreated HUVEC. Combinations of mAbs to ICAM-1 with either maltose-1-phosphate or heparin inhibited Mono Mac 6 adhesion to ox-LDL-stimulated HUVEC by more than 50%, while either alone had no effect. This suggests that two distinct endothelial ligands for Mac-1, inducible ICAM-1 and carbohydrate-decorated heparin-like proteoglycan structures mediate monocytic cell interaction with ox-LDL-treated HUVEC. The stimulating activity in ox-LDL could partly be transfered to bovine serum albumin, while lysophosphatidylcholine or 8-epi prostaglandin F2alpha produced no stimulatory effects. The inhibition of ox-LDL effects with the antioxidant PDTC indicates radicals as possible mediators. In conclusion, we show that oxidatively modified LDL induces adhesion of monocytic cells, which utilize at least two distinct adhesive receptors on endothelium, one being identified as ICAM-1.