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Updated: May 23, 2026
06:15
Quantification of Efferocytosis by Single-cell Fluorescence Microscopy
Published on: August 18, 2018
Extracellular histones inhibit efferocytosis
Arnaud Friggeri1, Sami Banerjee, Na Xie
1Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Molecular Medicine (Cambridge, Mass.)
|April 13, 2012
Summary
Extracellular histones, particularly H3 and H4, inhibit efferocytosis, the process of clearing apoptotic cells. This histone-mediated efferocytosis impairment may drive inflammation and tissue injury during acute inflammatory states.
Area of Science:
- Immunology
- Cell Biology
- Pathophysiology
Background:
- Efferocytosis is crucial for resolving inflammation by clearing apoptotic cells.
- Elevated extracellular histones are linked to acute inflammatory conditions and organ dysfunction.
Purpose of the Study:
- To investigate the role of extracellular histones in modulating efferocytosis.
- To elucidate the mechanism by which histones affect the clearance of apoptotic cells.
Main Methods:
- Assessed the impact of histones H1, H3, and H4 on macrophage phagocytosis of apoptotic cells in vitro.
- Examined histone H3 binding to macrophages and its modulation by opsonins (Gas6, MFG-E8) and integrins (α(v)β₅, α(v)β₃, Mer).
- Evaluated the effect of histone H3 on efferocytosis in vivo using alveolar macrophages and tested the efficacy of activated protein C in mitigating histone effects.
Main Results:
- Histones H3 and H4, but not H1, significantly reduced efferocytosis of apoptotic cells by macrophages.
- Histone H3 directly bound to macrophages, an interaction reduced by Gas6, MFG-E8, α(v)β₅ integrin, and Mer.
- Histone H3 impaired efferocytosis in vivo, an effect reversed by activated protein C, which degrades histones.
Conclusions:
- Extracellular histones inhibit efferocytosis, representing a novel mechanism contributing to acute inflammation.
- Histone-mediated efferocytosis impairment exacerbates organ system dysfunction and mortality in inflammatory states.
- Targeting histone degradation may offer a therapeutic strategy for inflammatory diseases.
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