Lysophosphatidylcholine: a chemotactic factor for human monocytes and its potential role in atherogenesis.

Abstract

Native low density lipoprotein (LDL) does not affect monocyte/macrophage motility. On the other hand, oxidatively modified LDL inhibits the motility of resident peritoneal macrophages yet acts as a chemotactic factor for circulating human monocytes. We now show that lysophosphatidylcholine (lyso-PtdCho), which is generated by a phospholipase A2 activity during LDL oxidation, is a potent chemotactic factor for monocytes. It is not chemotactic for neutrophils or for resident macrophages. Platelet-activating factor, after treatment with phospholipase A2, becomes chemotactic for monocytes, whereas the intact factor is not. Synthetic 1-palmitoyl-lyso-PtdCho showed chemotactic activity comparable to that of the lyso-PtdCho fraction derived from oxidized LDL. The results suggest that Iyso-PtdCho in oxidized LDL may favor recruitment of monocytes into the arterial wall during the early stages of atherogenesis. Generation of lyso-PtdCho, either from LDL itself or from membrane phospholipids of damaged cells, could play a more general role in inflammatory processes throughout the body.One of the characteristics of the earliest atherosclerotic lesion is the intimal accumulation of lipid-laden foam cells derived predominantly from monocyte/macrophages (1-5).Exactly how these cells are recruited and retained in the artery wall remains unclear, but it seems likely that adhesion molecules and chemotactic factors are involved. Although many different chemotactic factors for monocytes have been described (6-9), their relative importance in relation to atherogenesis remains to be determined. The possibility that a high plasma level of low density lipoprotein (LDL) might play a role in monocyte recruitment seemed attractive in view of the fact that a high LDL level is the proximate consequence of LDL receptor deficiency in homozygous familial hypercholesterolemia and, therefore, must somehow account for the genesis of the fatty streak lesions (10

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

“…A synthetic lysophosphatidyl choline, 1-palmitoyl-lysophosphatidyl choline, had comparable chemotactic activity with an optimum concentration at 25 txM [3,4]. Our experiments demonstrate that HNE is a strong chemoattractant for human monocytes at concentrations which can be found in oxidised LDL.…”

“…Quinn and co-workers have shown that oxidised LDL induces chemotaxis in human monocytes, with lysophosphatidyl choline being one of its active components [3,4]. Further, oxidised LDL has been shown to be toxic for a variety of cell types including smooth muscle cells, fibroblasts [5] and more recently mouse peritoneal macrophages [6,7], the macrophage-like cell line P388D1 [8] and human monocyte-macrophages [9].…”

Phospholipase A2 is a Major Component of the Salt‐Extractable Pool of Matrix Proteins in Adult Human Articular Cartilage

“…Lysophosphatidylcholine, a product of the PLA,-catalyzed hydrolysis of phospholipids, has been shown to be cytolytic and fusogenic (30). More recently, it has also been reported to be chemotactic for monocytes (31). Thus, uncontrolled activity of the resident PLA, in the cartilage matrix could have quite detrimental effects on the resident cells.…”

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

“…89,90 LPC has been shown to both increase production of proinflammatory cytokines, 69 and have anti-inflammatory effects such as inhibiting high-mobility group protein B1 (HMGB1) secretion(16 h post-treatment with LPC). 91 These effects are dependent on different receptors as well as cell types, but not yet fully understood.…”