Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells.
Accumulation of monocyte-derived foam cells in focal areas of the arterial intima is one of the key events in early atherogenesis. We have examined the effect of lysophosphatidylcholine (lyso-PC; lysolecithin), a major phospholipid component of atherogenic lipoproteins, on the expression of adhesion molecules for monocytes, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), in cultured human and rabbit arterial endothelial cells. Cultured rabbit aortic endothelial cells treated with lyso-PC showed increased mRNA and cell surface expression of VCAM-1 and ICAM-1, which was associated with increased adhesion of monocytes and monocyte-like cells (THP-1, U937). In cultured human iliac artery endothelial cells, lyso-PC similarly induced both VCAM-1 and ICAM-1, whereas in umbilical vein endothelial cells only ICAM-1 was up-regulated. In all endothelial cells examined, the effect of lyso-PC on E-selectin (endothelial-leukocyte adhesion molecule-1) expression was negligible, thus differentiating this stimulus from other endothelial activators, such as interleukin 1, tumor necrosis factor, or lipopolysaccharide. We conclude that lyso-PC can selectively induce VCAM-1 and ICAM-1 in arterial endothelial cells and that this action, in addition to its monocyte chemoattractant activity, may play an important role in monocyte recruitment into atherosclerotic lesions.
Kume
N
N
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Cybulsky
M I
MI
Gimbrone
M A
MA
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D010743:Phospholipids / Q000494:pharmacology; D011817:Rabbits; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1