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Published on: September 2, 2014
The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically?
Christopher D Gregory1, Andrew Devitt
1University of Edinburgh MRC Centre for Inflammation Research, College of Medicine and Veterinary Medicine, UK. chris.gregory@ed.ac.uk
Abstract:
Macrophages play important roles in the clearance of dying and dead cells. Typically, and perhaps simplistically, they are viewed as the professional phagocytes of apoptotic cells. Clearance by macrophages of cells undergoing apoptosis is a non-phlogistic phenomenon which is often associated with actively anti-inflammatory phagocyte responses. By contrast, macrophage responses to necrotic cells, including secondarily necrotic cells derived from uncleared apoptotic cells, are perceived as proinflammatory. Indeed, persistence of apoptotic cells as a result of defective apoptotic-cell clearance has been found to be associated with the pathogenesis of autoimmune disease. Here we review the mechanisms by which macrophages interact with, and respond to, apoptotic cells. We suggest that macrophages are especially important in clearing cells at sites of histologically visible, high-rate apoptosis and that, otherwise, apoptotic cells are removed largely by non-macrophage neighbours. We challenge the view that necrotic cells, including persistent apoptotic cells are, of necessity, proinflammatory and immunostimulatory and suggest that, under appropriate circumstances, persistent apoptotic cells can provide a prolonged anti-inflammatory stimulus.
Insights
Macrophages clear apoptotic cells, typically non-inflammatorily. However, uncleared cells can trigger inflammation, potentially linking to autoimmune disease. This review explores macrophage interactions with dying cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages are key in clearing dying cells, with apoptotic cell clearance generally being anti-inflammatory.
- Necrotic cells, including those from uncleared apoptotic cells, are often considered pro-inflammatory.
- Defective apoptotic cell clearance is implicated in autoimmune disease pathogenesis.
Purpose of the Study:
- To review mechanisms of macrophage interaction with apoptotic cells.
- To challenge the view that necrotic cells are always pro-inflammatory.
- To explore the role of persistent apoptotic cells in inflammation.
Main Methods:
- Literature review of macrophage-apoptotic cell interactions.
- Analysis of inflammatory responses to different cell death modalities.
- Discussion of the role of macrophages in high-rate apoptosis sites versus general clearance.
Main Results:
- Macrophages are crucial for clearing cells at sites of high-rate apoptosis.
- Non-macrophage neighbors often handle general apoptotic cell clearance.
- Persistent apoptotic cells may provide prolonged anti-inflammatory stimuli under certain conditions.
Conclusions:
- Macrophage roles in cell clearance are nuanced, varying with apoptosis rate and cell type.
- The pro-inflammatory nature of necrotic cells is context-dependent.
- Persistent apoptotic cells might offer therapeutic anti-inflammatory potential.
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