Influence of native and modified lipoproteins on migration of mouse peritoneal macrophages and the effect of the antioxidants vitamin E and Probucol.
Macrophage-derived foam cells are a key component of the atherosclerotic plaque. Stimulation of the migration of foam cells back to the blood potentially offers an approach to plaque regression. However, information on the natural and synthetic factors influencing macrophage migration remains limited. The aim of the present study was to determine the effects of different lipoproteins and antioxidants on the migration of mouse peritoneal macrophages and macrophage-derived foam cells. The migration of cells was determined in vitro by using a Boyden chamber. Cellular content of cholesterol and cholesteryl esters was measured by HPLC. The native lipoproteins, VLDL, LDL, and HDL, and the chemically modified lipoproteins acetylated LDL (acLDL) and oxidized LDL (oxLDL), all acted as chemoattractants for macrophages that had not been lipid-loaded. The antioxidants vitamin E and Probucol had chemoattractive and chemokinetic effects on the migration of unloaded mouse peritoneal macrophages. Foam cells (lipid-laden macrophages) showed decreased mobility with increased cellular lipid content. However, as macrophages accumulated higher amounts of cholesterol and cholesteryl esters, the additional decrease of cell migration was relatively minor. Simultaneous incubation of macrophages with acLDL and vitamin E or Probucol increased migration. The content of cellular cholesterol and cholesteryl esters was not changed when acLDL-treated cells were exposed at the same time to vitamin E, but cholesteryl ester content was increased in the presence of Probucol. Overall, the findings indicate that the antioxidants vitamin E and Probucol have a potential anti-atherogenic action in stimulating migration of lipid-laden macrophages without major impairment of the ability of the cells to accumulate and metabolize modified LDL.
Department of Pharmacology, Merz & Co. GmbH, Frankfurt a.M./Germany.
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D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D008074:Lipoproteins / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D011341:Probucol / Q000494:pharmacology*; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology*
D002788:Cholesterol Esters; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D002784:Cholesterol; D011341:Probucol