Journal article
Efferocytosis perpetuates substance accumulation inside macrophage populations
- Abstract:
- In both cells and animals, cannibalism can transfer harmful substances from the consumed to the consumer. Macrophages are immune cells that consume their own dead via a process called cannibalistic efferocytosis. Macrophages that contain harmful substances are found at sites of chronic inflammation, yet the role of cannibalism in this context remains unexplored. Here we take mathematical and experimental approaches to study the relationship between cannibalistic efferocytosis and substance accumulation in macrophages. Through mathematical modelling, we deduce that substances which transfer between individuals through cannibalism will concentrate inside the population via a coalescence process. This prediction was confirmed for macrophage populations inside a closed system. We used image analysis of whole slide photomicrographs to measure both latex microbead and neutral lipid accumulation inside murine bone marrow-derived macrophages (104–105 cells) following their stimulation into an inflammatory state ex vivo. While the total number of phagocytosed beads remained constant, cell death reduced cell numbers and efferocytosis concentrated the beads among the surviving macrophages. As lipids are also conserved during efferocytosis, these cells accumulated lipid derived from the membranes of dead and consumed macrophages (becoming macrophage foam cells). Consequently, enhanced macrophage cell death increased the rate and extent of foam cell formation. Our results demonstrate that cannibalistic efferocytosis perpetuates exogenous (e.g. beads) and endogenous (e.g. lipids) substance accumulation inside macrophage populations. As such, cannibalism has similar detrimental consequences in both cells and animals.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.8MB, Terms of use)
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- Publisher copy:
- 10.1098/rspb.2019.0730
Authors
- Publisher:
- Royal Society
- Journal:
- Proceedings of the Royal Society B: Biological Sciences More from this journal
- Volume:
- 286
- Issue:
- 1904
- Article number:
- 20190730
- Publication date:
- 2019-06-02
- Acceptance date:
- 2019-05-12
- DOI:
- EISSN:
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1471-2954
- ISSN:
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0962-8452
- Language:
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English
- Keywords:
- Pubs id:
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pubs:1012020
- UUID:
-
uuid:aa18d727-03ba-4473-b737-c21ffd5c8808
- Local pid:
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pubs:1012020
- Source identifiers:
-
1012020
- Deposit date:
-
2019-06-12
Terms of use
- Copyright holder:
- Ford et al
- Copyright date:
- 2019
- Notes:
- © 2019 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License, which permits unrestricted use, provided the original author and source are credited.
- Licence:
- CC Attribution (CC BY)
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