Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells.

Abstract

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-i (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-i) 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. (J. Clin. Invest. 1992. 90:1138-1144 Key word: atherosclerosis * intercellular adhesion molecule-1 * inflammation * oxidized low density lipoprotein * vascular cell adhesion molecule-1

Lysophosphatidylcholine is a natural adjuvant that initiates cellular immune responses

“…LPC is a chemoattractant, enhancing the recruitment of monocytes, neutrophils and lymphocytes [13,19,27]. Hence, elevated levels of LPC in inflamed tissues may enhance the recruitment of blood monocytes and their differentiation to mature DC as previously shown in vitro [8].…”

“…It is a potent chemoattractant for monocytes [13] phagocytes [14] and T lymphocytes [15,16]. It stimulates the expression of growth factor and adhesion molecules by endothelial cells [17][18][19] as well as their production of monocyte chemoattractant protein-1 [20]. LPC can activate monocytes and macrophages [21][22][23][24][25] and is one of the intracellular mediators required in the cytotoxic response of human NK cells to tumour cells [26].…”

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE − /− /ICAM-1 − /− ) Fed a Fat or a Chow Diet

“…40 Upregulation of ICAM-1 in cultured human and rabbit arterial endothelial cells has been shown to occur after lysophosphatidylcholine treatment. 41 Moreover, lysophosphatidylcholine induced the expression of ICAM-1 on endothelium derived from human iliac arteries but not from Values are meanϮSEM (n) and express ratio (%) of lesion area to media area (measured in 2 ). P values are shown for ApoE Ϫ/Ϫ (SKO) and ApoE Ϫ/Ϫ /ICAM-1 Ϫ/Ϫ (DKO) mice fed a chow or fat diet from 0 to 20 weeks.…”

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte‐macrophages

“…Furthermore, minimally-modified LDL stimulates endothelial cells and smooth muscle cells to express a monocyte-specific chemoattractant, MCP-1 [33]. Oxidised LDL stimulates the expression of P-selectin by rat endothelial cells [34], facilitating leukocyte-endothelium interactions, and lysophosphatidyl choline, which was reported to selectively attract monocytes [4], stimulates the expression of leukocyte-adhesion molecules ICAM-1 and VCAM-1 on rat and human endothelial cells [35].…”