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Oxidized lipoprotein (a) induces cell adhesion molecule Mac-1 (CD 11b) and enhances adhesion of the monocytic cell line U937 to cultured endothelial cells. 1996

M S Ragab, and P Selvaraj, and D S Sgoutas
Department of Pathology and Laboratory Medicine, School of Medicine, Emory University Hospital, Atlanta, GA 30322, USA.

Because of structural similarities between low density lipoproteins (LDL) and lipoprotein (a) (Lp(a)), we have investigated the properties and the functional activities of oxidized Lp(a) and focused on whether oxidized Lp(a), like oxidized LDL, can induce monocyte differentiation and adhesion of monocytic cells to endothelial cells grown in culture. Oxidized Lp(a), prepared in vitro by cupric ion oxidation, gave absorption curves of conjugated dienes with a lag-phase of 61.7 +/- 6.6 min (mean +/- S.D.) as compared to 85.2 +/- 7.2 min (n = 6, P < 0.01) for oxidized LDL from the same donors and at equimolar concentrations. Degradation of oxidized 125I Lp(a) by the monocytic cell line U937 at 37 degrees C was 1.6 +/- 0.3 nmol/g of cell protein, significantly (P < 0.01) greater than the degradation of oxidized 125I-LDL, which was 1.15 +/- 0.2 nmol/g of cell protein. Equimolar concentrations of oxidized Lp(a) and LDL inhibited the growth of U937 by 82 +/- 8.2% and 64 +/- 7.1%, respectively, when compared with the effect (negligible) produced by native Lp(a) and LDL. In addition, equimolar concentrations of oxidized Lp(a) and LDL induced adhesion molecule, Mac-1 (CD 11b), expression in U937 by 64 +/- 7.1% and 58 +/- 6.1% (P > 0.05), respectively, of the effect produced by phorbol esters (PMA) (P < 0.01). U937 cells incubated with oxidized Lp(a) and LDL, showed an adherence to cultured endothelial cells at 42 +/- 5.2% and 34 +/- 4.8%, respectively (P < 0.05), of the adherence shown by the same cells activated by PMA (P < 0.01). Our results suggest that oxidized Lp(a) like oxidized LDL plays an important role in the development of atherogenesis by inducing adhesion of monocytes to the arterial intimal and by stimulating intimal monocytes to differentiate into macrophages.

UI MeSH Term Description Entries
D008315 Malondialdehyde The dialdehyde of malonic acid. Malonaldehyde,Propanedial,Malonylaldehyde,Malonyldialdehyde,Sodium Malondialdehyde,Malondialdehyde, Sodium
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003300 Copper A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55. Copper-63,Copper 63
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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