Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Tessa J Barrett
Division of Cardiology, NYU School of Medicine, New York, United States; Department of Medicine, NYU School of Medicine, New York, United States; Marc and Ruti Bell Program in Vascular Biology, NYU School of Medicine, New York, United States
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Eileen McNeill
Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom; John Radcliffe Hospital, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
Arun Manmadhan
Division of Cardiology, NYU School of Medicine, New York, United States; Department of Medicine, NYU School of Medicine, New York, United States; Marc and Ruti Bell Program in Vascular Biology, NYU School of Medicine, New York, United States
Carlota Recio
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Alfredo Carmineri
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Maximillian H Brodermann
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Gemma E White
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Dianne Cooper
William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
Joseph A DiDonato
Department of Cellular and Molecular Medicine, Lerner Research Institute of the Cleveland Clinic, Cleavland, United States
Maryam Zamanian-Daryoush
Department of Cellular and Molecular Medicine, Lerner Research Institute of the Cleveland Clinic, Cleavland, United States
Stanley L Hazen
Department of Cellular and Molecular Medicine, Lerner Research Institute of the Cleveland Clinic, Cleavland, United States
Keith M Channon
Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom; John Radcliffe Hospital, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
David R Greaves
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Division of Cardiology, NYU School of Medicine, New York, United States; Department of Medicine, NYU School of Medicine, New York, United States; Marc and Ruti Bell Program in Vascular Biology, NYU School of Medicine, New York, United States
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.
