title: Acute exposure to apolipoprotein A1 inhibits macrophage chemotaxis in vitro and monocyte recruitment in vivo.
abstract: 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.
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Asif J
authors: 0000-0002-3224-3651
authors: AJ
authors: Iqbal
authors: 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.
authors: Tessa J
authors: TJ
authors: Barrett
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Lewis
authors: 0000-0003-4622-9890
authors: L
authors: Taylor
authors: 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.
authors: Eileen
authors: E
authors: McNeill
authors: 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.
authors: Arun
authors: A
authors: Manmadhan
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Carlota
authors: C
authors: Recio
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Alfredo
authors: A
authors: Carmineri
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Maximillian H
authors: MH
authors: Brodermann
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Gemma E
authors: GE
authors: White
authors: William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
authors: Dianne
authors: D
authors: Cooper
authors: Department of Cellular and Molecular Medicine, Lerner Research Institute of the Cleveland Clinic, Cleavland, United States.
authors: Joseph A
authors: JA
authors: DiDonato
authors: Department of Cellular and Molecular Medicine, Lerner Research Institute of the Cleveland Clinic, Cleavland, United States.
authors: Maryam
authors: M
authors: Zamanian-Daryoush
authors: Department of Cellular and Molecular Medicine, Lerner Research Institute of the Cleveland Clinic, Cleavland, United States.
authors: Stanley L
authors: SL
authors: Hazen
authors: 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.
authors: Keith M
authors: KM
authors: Channon
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: David R
authors: DR
authors: Greaves
authors: 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.
authors: Edward A
authors: 0000-0001-9802-143X
authors: EA
authors: Fisher
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D010538:Peritonitis / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016632:Apolipoprotein A-I; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: apolipoprotein; cell biology; chemokines; chemotaxis; human; immunology; macrophages; mouse