Downregulation by tumor necrosis factor-α of monocyte CCR2 expression and monocyte chemotactic protein-1-induced transendothelial migration is antagonized by oxidized low-density lipoprotein

作者: Christian Weber , Georg Draude , Kim S.C. Weber , Joachim Wübert , Reinhard L. Lorenz

DOI: 10.1016/S0021-9150(99)00021-0

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摘要: The subintimal infiltration with monocytes is crucially involved in the development of complex atherosclerotic plaques. Monocyte chemotactic protein-1 (MCP-1) and its receptor CCR2 are important for monocyte extravasation formation lesions. However, mechanisms persistence plaques remain to be elucidated. Flow cytometric analysis revealed that monocytoid Mono Mac 6 cells had transmigrated endothelium towards a MCP-1 gradient expressed higher levels than non-migratory fraction, while input were intermediate, suggesting high essential transendothelial chemotaxis. Pretreatment or isolated human blood inflammatory cytokine tumor necrosis factor (TNF)-alpha dose- time-dependently reduced MCP-1-induced chemotaxis, which was inhibited by antagonist 9-76 analog. This paralleled decrease surface protein mRNA expression. as assessed flow cytometry reverse transcription-polymerase chain reaction, inferring inhibition transmigration due downregulation insufficient In contrast, treatment oxidized low-density (oxLDL) containing lipids, such cholesteryl linoleate 13-hydroxide. but not LDL, increased Notably, oxLDL counteracted TNF-alpha-mediated CCR2-dependent Macrophage-colony-stimulating hardly affected expression function, differentiation responsible effects on CCR2. conclusion, TNF-alpha impairs migration downregulating appears critical migration. Exposure antagonized TNF-alpha, may thus contribute retention perpetuation chronic reaction unstable

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