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

Atherosclerosis
W ErlChristian Weber

Abstract

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 a...Continue Reading

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