Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol

• DOI: 10.1194/jlr.m006486
• Publication Date: 2010-07-23T00:37:52Z
• Authors: Xuewei Zhu; John S. Owen; Martha D. Wilson; Haitao Li; Gary L. Griffiths; Michael J. Thomas; Elizabeth M. Hilt...; Michael B. Fessler; John S. Parks
• Keywords: Lipid raft

We previously showed that macrophages from macrophage-specific ATP-binding cassette transporter A1 (ABCA1) knockout (Abca1(-M/-M)) mice had an enhanced proinflammatory response to the Toll-like receptor (TLR) 4 agonist, lipopolysaccharide (LPS), compared with wild-type (WT) mice. In present study, we demonstrate a direct association between free cholesterol (FC), lipid raft content, and hyper-responsiveness of LPS in WT Abca1(-M/-M) were also hyper-responsive specific agonists TLR2, TLR7, TLR9, but not TLR3, macrophages. hypothesized ABCA1 regulates macrophage responsiveness TLR by modulation mobilization rafts. demonstrated vs. contained 23% more FC isolated Further, mass spectrometric analysis suggested phospholipid composition was unchanged. Although cell surface expression TLR4 similar macrophages, significantly distributed membrane rafts exhibited increased trafficking predominantly intracellular TLR9 into TLR9-specific agonist (CpG). Collectively, our data suggest dampens inflammation reducing MyD88-dependent TLRs selective reduction content