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Cited by 16Phagocytosis and Immune RegulationCell death mechanisms and regulationNeuroinflammation and Neurodegeneration Mechanisms

CX3CL1(+) Microparticles-Induced MFG-E8 Enhances Apoptotic Cell Clearance by Alveolar Macrophages

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Tsai, Wen-Hui, Chang, Shao-Chi, Lin, Yu-Chieh, Hsu, Hui-Chi·2021·Cells
DOI 10.3390/cells10102583PMC PMC8533702
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Abstract

During the resolution phase of acute lung injury, apoptotic cells release CX3CL1 as a “find-me” signal to attract alveolar macrophage transmigration toward apoptotic cells for phagocytosis. However, it is still not clear whether CX3CL1 has pro-phagocytic activity on alveolar macrophage. In this study, we investigated the role of apoptotic NB4 cells-derived CX3CL1(+) microparticles (apo-MP) on the phagocytic activity of NR8383 cells. We demonstrate that exogenous CX3CL1 and apo-MP enhanced the phagocytic activity of NR8383 cells in a CX3 CR1-dependent manner. The apo-MP-enhanced phagocytic activity on NR8383 was attenuated when apo-MP and NR8383 cells were pre-treated with anti-CX3CL1 antibodies and anti-CX3CR1 antibody, respectively, before incubating both for phagocytic assay. Further studies demonstrate that exogenous CX3CL1 and apo-MP also enhanced NR8383 cells in their surface expression and release of MFG-E8 in a CX3CR1 dependent manner. The enhanced phagocytic activity of CX3CL1-treated NR8383 cells was attenuated when NR8383 cells were pre-treated with an anti-MFG-E8 antibody before CX3CL1 treatment. We conclude that apoptotic cell-derived CX3CL1(+) microparticles enhance the phagocytic activity of NR8383 cells by up-regulating their MFG-E8 as a bridge molecule, and these contribute to the formation of phagocytic synapses between apoptotic cells and alveolar macrophages for the subsequent phagocytic clearance of apoptotic cells.

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  • Macrophages preferentially efferocytose cancer cells, and significant efforts are being made to inhibit efferocytosis therapeutically.

    “Indeed, macrophage cell therapy has faced a significant hurdle in that macrophages preferentially efferocytose cancer cells, and significant efforts are being made to inhibit efferocytosis therapeutically (37, 38).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [38]

    The Results (§3.1 and §3.5; page unavailable) show alveolar macrophages engulfing apoptotic leukemic NB4 cells more readily than viable NB4 cells. They do not establish a preference for cancer cells over other cell types or discuss macrophage cell therapy. The Discussion (§4; page unavailable) focuses on enhancing efferocytosis, not therapeutic efforts to inhibit it. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Colorectal cancer APC oncogene increased plasma membrane cholesterol and thus WNT signaling hubs (lipid rafts).

    “Another example comes from colorectal cancer where the APC oncogene increased plasma membrane cholesterol and thus WNT signaling hubs (lipid rafts) (38).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [38]

    The Introduction and Results section 3.2 discuss acute promyelocytic leukemia and macrophage clearance of apoptotic cells, not colorectal cancer. Searches for APC, plasma-membrane cholesterol, WNT signaling, and lipid rafts found no passage addressing the claim in our copy; page numbers were unavailable. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Tsai, W.-H., Chang, S.-C., Lin, Y.-C., & Hsu, H.-C.
Affiliations
  • Taipei Medical University (TW)
  • National Yang Ming Chiao Tung University (TW)
Corresponding author
Hsu, Hui-Chi
ORCID
Tsai, Wen-Hui
Venue
Cells
Publisher
MDPI AG
Published
2021-09-28
Volume
10
Issue
10
Pages
2583
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells10102583
PMC
PMC8533702
OpenAlex
W3203147724
Cited by
16
References
6
Citations by year
2026: 5 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 1
FWCI
0.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Council (NSC-101-2314-B-010 -026)
  • Taipei Veterans General Hospital (V102C-050)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
fractalkine, microparticles, MFG-E8, efferocytosis, alveolar macrophages, phagocytosis, CX3CR1, apoptotic cells
MeSH terms
Antigens, Surface, Humans, Milk Proteins, Macrophages, Alveolar, Apoptosis, Chemokine CX3CL1, Cell-Derived Microparticles

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