Cited by 314Phagocytosis and Immune RegulationAutophagy in Disease and TherapyCell death mechanisms and regulation

The clearance of dying cells: table for two

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Green, D R, Oguin, T H, Martinez, J·2016·Cell Death & Differentiation

Abstract

Phagocytic cells of the immune system must constantly survey for, recognize, and efficiently clear the billions of cellular corpses that arise as a result of development, stress, infection, or normal homeostasis. This process, termed efferocytosis, is critical for the prevention of autoimmune and inflammatory disorders, and persistence of dead cells in tissue is characteristic of many human autoimmune diseases, notably systemic lupus erythematosus. The most notable characteristic of the efferocytosis of apoptotic cells is its 'immunologically silent' response. Although the mechanisms by which phagocytes facilitate engulfment of dead cells has been a well-studied area, the pathways that coordinate to process the ingested corpse and direct the subsequent immune response is an area of growing interest. The recently described pathway of LC3 (microtubule-associated protein 1A/1B-light chain 3)-associated phagocytosis (LAP) has shed some light on this issue. LAP is triggered when an extracellular particle, such as a dead cell, engages an extracellular receptor during phagocytosis, induces the translocation of autophagy machinery, and ultimately LC3 to the cargo-containing phagosome, termed the LAPosome. In this review, we will examine efferocytosis and the impact of LAP on efferocytosis, allowing us to reimagine the impact of the autophagy machinery on innate host defense mechanisms.

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Crossref · 10.1038/cdd.2015.172

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  • Apoptotic cells retain plasma membrane integrity and metabolic activity as the process proceeds to completion, allowing rapid clearance by macrophages or other phagocytic cells (efferocytosis).

    “Apoptotic cells retain plasma membrane integrity and metabolic activity (to some degree) as the process proceeds to completion, which—in vivo—allows for the rapid clearance by macrophages or other cells with phagocytic activity (a process commonly known as efferocytosis) [35].”
  • Defective efferocytosis or dysfunctional apoptotic-cell receptors, especially during non-resolving inflammation, leads to autoimmunity, tissue necrosis and pathological inflammation.

    “Not surprisingly, when efferocytosis becomes defective or when apoptotic cell receptors become dysfunctional (predominantly during non-resolving inflammation), autoimmunity, tissue necrosis and pathological inflammation ensue187.”

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  1. Martinez J, Malireddi RK, Lu Q, Cunha LD, Pelletier S, Gingras S et al. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol 2015; 17: 893-906.

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Authors
Green, D. R., Oguin, T. H., & Martinez, J.
Affiliations
  • St. Jude Children's Research Hospital (US)
  • National Institutes of Health (US)
Corresponding author
Martinez, J
Venue
Cell Death & Differentiation
Published
2016-03-18
Volume
23
Issue
6
Pages
915-926
ISSN
  • 1350-9047 (ISSN-L)
  • 1476-5403
OpenAlex
W2297172779
Cited by
314
References
207
Citations by year
2026: 18 · 2025: 26 · 2024: 30 · 2023: 32 · 2022: 40 · 2021: 41 · 2020: 35 · 2019: 28 · 2018: 26 · 2017: 26 · 2016: 12
FWCI
2.96
Type
journal article
Language
en
Open access
Locations
  • Cell Death and Differentiation (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI040646)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
efferocytosis, LC3-associated phagocytosis, autophagy machinery, phagocytes, systemic lupus erythematosus, autoimmune disease, innate immunity
MeSH terms
Autophagy-Related Proteins, Animals, Autoimmune Diseases, Humans, Inflammation, Microtubule-Associated Proteins, Phagocytes, Phagocytosis, Signal Transduction, Cytokines, Apoptosis, Reactive Oxygen Species

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