Acute exposure to apolipoprotein A1 inhibits macrophage chemotaxis in vitro and monocyte recruitment in vivo

• Published in: eLife Vol. 5
• Main Authors: Iqbal, Asif J, Barrett, Tessa J, Taylor, Lewis, McNeill, Eileen, Manmadhan, Arun, Recio, Carlota, Carmineri, Alfredo, Brodermann, Maximillian H, White, Gemma E, Cooper, Dianne, DiDonato, Joseph A, Zamanian-Daryoush, Maryam, Hazen, Stanley L, Channon, Keith M, Greaves, David R, Fisher, Edward A
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 30-08-2016; eLife Sciences Publications, Ltd
• Subjects: 1-Phosphatidylinositol 3-kinase; Actin; Adoptive transfer; AKT protein; Animals; Anti-inflammatory agents; apolipoprotein; Apolipoprotein A-I - metabolism; Apolipoproteins; Cell Biology; Chemokines; Chemotactic factors; Chemotaxis; Chemotaxis - drug effects; Cytoskeleton; Disease Models, Animal; High density lipoprotein; Humans; Immunology; Inflammation; Kinases; Leukocyte migration; Lipid rafts; Macrophages; Macrophages - cytology; Macrophages - drug effects; Medicine; Mice; Microscopy; Monocytes; Peritonitis; Peritonitis - pathology; Phosphatidylinositol 3-Kinase - metabolism; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Statistical analysis; Variance analysis; mouse; apolipoprotein; macrophages; cell biology; chemokines; human; immunology; chemotaxis
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.15190

Apolipoprotein A1 (apoA1) is the major protein component of high-density lipoprotein (HDL) and has well documented anti-inflammatory properties. To better understand the cellular and molecular basis of the anti-inflammatory actions of apoA1, we explored the effect of acute human apoA1 exposure on the migratory capacity of monocyte-derived cells in vitro and in vivo. Acute (20-60 min) apoA1 treatment induced a substantial (50-90%) reduction in macrophage chemotaxis to a range of chemoattractants. This acute treatment was anti-inflammatory in vivo as shown by pre-treatment of monocytes prior to adoptive transfer into an on-going murine peritonitis model. We find that apoA1 rapidly disrupts membrane lipid rafts, and as a consequence, dampens the PI3K/Akt signalling pathway that coordinates reorganization of the actin cytoskeleton and cell migration. Our data strengthen the evidence base for therapeutic apoA1 infusions in situations where reduced monocyte recruitment to sites of inflammation could have beneficial outcomes.