Acute exposure to apolipoprotein A1 inhibits macrophage chemotaxis in vitro and monocyte recruitment in vivo
- University of Oxford, United Kingdom
- NYU School of Medicine, United States
- Queen Mary University of London, United Kingdom
- Lerner Research Institute of the Cleveland Clinic, United States
- 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.
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Author details
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)
- 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.
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.
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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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
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