Apolipoprotein A-I mimetic 4F alters the function of human monocyte-derived macrophages

Lesley E. Smythies, C. Roger White, Akhil Maheshwari, M. N. Palgunachari, G. M. Anantharamaiah, Manjula Chaddha, Ashish R. Kurundkar, Geeta Datta

Research output: Contribution to journalArticle

Abstract

HDL and its major protein component apolipoprotein A-I (apoA-I) exert anti-inflammatory effects, inhibit monocyte chemotaxis/adhesion, and reduce vascular macrophage content in inflammatory conditions. In this study, we tested the hypothesis that the apoA-I mimetic 4F modulates the function of monocyte-derived macrophages (MDMs) by regulating the expression of key cell surface receptors on MDMs. Primary human monocytes and THP-1 cells were treated with 4F, apoA-I, or vehicle for 7 days and analyzed for expression of cell surface markers, adhesion to human endothelial cells, phagocytic function, cholesterol efflux capacity, and lipid raft organization. 4F and apoA-I treatment decreased the expression of HLA-DR, CD86, CD11b, CD11c, CD14, and Toll-like receptor-4 (TLR-4) compared with control cells, suggesting the induction of monocyte differentiation. Both treatments abolished LPS-induced mRNA for monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1), regulated on activation, normal T-expressed and presumably secreted (RANTES), IL-6, and TNF-α but significantly upregulated LPS-induced IL-10 expression. Moreover, 4F and apoA-I induced a 90% reduction in the expression of CD49d, a ligand for the VCAM-1 receptor, with a concurrent decrease in monocyte adhesion (55% reduction) to human endothelial cells and transendothelial migration (34 and 27% for 4F and apoA-I treatments) compared with vehicle treatment. In addition, phagocytosis of dextran-FITC beads was inhibited by 4F and apoA-I, a response associated with reduced expression of CD32. Finally, 4F and apoA-I stimulated cholesterol efflux from MDMs, leading to cholesterol depletion and disruption of lipid rafts. These data provide evidence that 4F, similar to apoA-I, induces profound functional changes in MDMs, possibly due to differentiation to an anti-inflammatory phenotype.

Original languageEnglish (US)
Pages (from-to)C1538-C1548
JournalAmerican Journal of Physiology - Cell Physiology
Volume298
Issue number6
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Keywords

  • Adhesion
  • Anti-inflammatory
  • Cytokines
  • High-density lipoprotein
  • Phagocytosis

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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  • Cite this

    Smythies, L. E., Roger White, C., Maheshwari, A., Palgunachari, M. N., Anantharamaiah, G. M., Chaddha, M., Kurundkar, A. R., & Datta, G. (2010). Apolipoprotein A-I mimetic 4F alters the function of human monocyte-derived macrophages. American Journal of Physiology - Cell Physiology, 298(6), C1538-C1548. https://doi.org/10.1152/ajpcell.00467.2009