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

  1. Asif J Iqbal
  2. Tessa J Barr
  3. Lewis Taylor
  4. Eileen McNeill
  5. Arun Manmadhan
  6. Carlota Recio
  7. Alfredo Carmineri
  8. Maximillian H Brodermann
  9. Gemma E White
  10. Dianne Cooper
  11. Joseph A DiDonato
  12. Stanley L Hazen
  13. Keith M Channon
  14. David R Greaves  Is a corresponding author
  15. Edward A Fisher  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. NYU School of Medicine, United States
  3. Queen Mary University of London, United Kingdom
  4. Lerner Research Institute of the Cleveland Clinic, United States
  5. University of Oxford, United States

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.

Article and author information

Author details

  1. Asif J Iqbal

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3224-3651
  2. Tessa J Barr

    Division of Cardiology, NYU School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Lewis Taylor

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4622-9890
  4. Eileen McNeill

    Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Arun Manmadhan

    Division of Cardiology, NYU School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Carlota Recio

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Alfredo Carmineri

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Maximillian H Brodermann

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Gemma E White

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Dianne Cooper

    William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Joseph A DiDonato

    Department of Cellular and Molecular Medicine, Lerner Research Institute of the Cleveland Clinic, Cleavland, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Stanley L Hazen

    Department of Cellular and Molecular Medicine, Lerner Research Institute of the Cleveland Clinic, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Keith M Channon

    Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. David R Greaves

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United States
    For correspondence
    david.greaves@path.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  15. Edward A Fisher

    Division of Cardiology, NYU School of Medicine, New York, United States
    For correspondence
    Edward.Fisher@nyumc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9802-143X

Funding

British Heart Foundation (RG/10/15/28578, PG/10/6028496, RG/15/10/31485)

  • Asif J Iqbal
  • Eileen McNeill
  • Keith M Channon
  • David R Greaves

Royal Society (IE120747)

  • David R Greaves
  • Edward A Fisher

National Institutes of Health (HL098055, DK095684)

  • Tessa J Barr
  • Edward A Fisher

BHF Centre of Research Excellence, Oxford (RE/08/004/23915)

  • Asif J Iqbal
  • David R Greaves

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Christopher K Glass, University of California, San Diego, United States

Ethics

Animal experimentation: UK animal studies were conducted with ethical approval from the Dunn School of Pathology Local Ethical Review Committee and in accordance with the UK Home Office regulations (Guidance on the Operation of Animals, Scientific Procedures Act, 1986). All USA animal experiments were carried out according to the guidelines of the National Institutes of Health and approved by the New York University Institutional Animal Care and Use Committee (Protocol 102090)

Human subjects: Human blood from anonymous healthy donors was obtained in the form of leukocyte cones from the NHS Blood and Transplant service. Leukocyte cones contain waste leukocytes isolated from individuals donating platelets via apharesis, and consist of a small volume (~10ml) of packed leukocytes with few red blood cells or platelets.

Version history

  1. Received: February 11, 2016
  2. Accepted: August 29, 2016
  3. Accepted Manuscript published: August 30, 2016 (version 1)
  4. Accepted Manuscript updated: September 2, 2016 (version 2)
  5. Accepted Manuscript updated: September 6, 2016 (version 3)
  6. Version of Record published: September 20, 2016 (version 4)

Copyright

© 2016, Iqbal et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Asif J Iqbal
  2. Tessa J Barr
  3. Lewis Taylor
  4. Eileen McNeill
  5. Arun Manmadhan
  6. Carlota Recio
  7. Alfredo Carmineri
  8. Maximillian H Brodermann
  9. Gemma E White
  10. Dianne Cooper
  11. Joseph A DiDonato
  12. Stanley L Hazen
  13. Keith M Channon
  14. David R Greaves
  15. Edward A Fisher
(2016)
Acute exposure to apolipoprotein A1 inhibits macrophage chemotaxis in vitro and monocyte recruitment in vivo
eLife 5:e15190.
https://doi.org/10.7554/eLife.15190

Share this article

https://doi.org/10.7554/eLife.15190

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