Journal article
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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.2MB, Terms of use)
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- Publisher copy:
- 10.7554/eLife.15190
Authors
+ Royal Society
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- Funder identifier:
- https://ror.org/03wnrjx87
- Funding agency for:
- Greaves, DR
- Fisher, EA
- Grant:
- IE120747
+ National Institutes of Health
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- Funder identifier:
- https://ror.org/01cwqze88
- Funding agency for:
- Barrett, TJ
- Fisher, EA
- Grant:
- DK095684
- HL098055
+ British Heart Foundation
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- Funder identifier:
- https://ror.org/02wdwnk04
- Funding agency for:
- Iqbal, AJ
- McNeill, E
- Channon, KM
- Greaves, DR
- Grant:
- RG/15/10/31485
- RG/10/15/28578
- PG/10/6028496
+ BHF Centre of Research Excellence, Oxford
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- Funding agency for:
- Iqbal, AJ
- Greaves, DR
- Grant:
- RE/08/004/23915
- Publisher:
- eLife Sciences Publications
- Journal:
- eLife More from this journal
- Volume:
- 5
- Article number:
- e15190
- Publication date:
- 2016-08-30
- Acceptance date:
- 2016-08-29
- DOI:
- EISSN:
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2050-084X
- Pmid:
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27572261
- Language:
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English
- Keywords:
- Pubs id:
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pubs:593527
- UUID:
-
uuid:c83dc24c-4a51-4484-b3f1-1e7681c894db
- Local pid:
-
pubs:593527
- Source identifiers:
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593527
- Deposit date:
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2016-09-20
- ARK identifier:
Terms of use
- Copyright holder:
- Iqbal et al.
- Copyright date:
- 2016
- Rights statement:
- © 2016, Iqbal et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
- Licence:
- CC Attribution (CC BY)
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