Oxidized phosphatidylserine–CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells
Open accessAbstract
The phagocytosis of apoptotic cells within an organism is a critical terminal physiological process in programmed cell death. Evidence suggests that apoptotic cell engulfment and removal by macrophages is facilitated by phosphatidylserine (PS) displayed at the exofacial surface of the plasma membrane; however, neither the macrophage receptors responsible for PS recognition, nor characterization of the PS molecular species potentially involved, have been clearly defined. We show that the class B scavenger receptor CD36 plays an essential role in macrophage clearance of apoptotic cells in vivo. Further, macrophage recognition of apoptotic cells via CD36 is shown to occur via interactions with membrane-associated oxidized PS (oxPS) and, to a lesser extent, oxidized phosphatidylcholine, but not nonoxidized PS molecular species. Mass spectrometry analyses of oxPS species identify structures of candidate ligands for CD36 in apoptotic membranes that may facilitate macrophage recognition. Collectively, these results identify oxPS-CD36 interactions on macrophages as potential participants in a broad range of physiologic processes where macrophage-mediated engulfment of apoptotic cells is involved.
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Phosphatidylserine and phosphatidylethanolamine are known to play important roles in macrophage mobility, phagocytosis, and apoptosis.
“these lipid subspecies are known to play important roles in Mθ mobility, phagocytosis, and apoptosis (Greenberg et al., 2006; Marino and Kroemer, 2013; Shiratsuchi et al., 1998).”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Greenberg et al., 2006
The Abstract reports that oxidized phosphatidylserine helps macrophages recognize and engulf apoptotic cells, supporting the phagocytosis and apoptosis-related portion of the claim. The cited passages do not establish a role for phosphatidylethanolamine or for either lipid in macrophage mobility; they also distinguish oxidized from nonoxidized phosphatidylserine. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCD36 functions in OS membrane uptake during normal conditions, also recognizes oxidized phospholipids, and may be functionally advantageous under oxidative stress as an aid for the MERTK pathway.
“Although CD36 functions in OS membrane uptake during normal conditions (Ryeom et al., 1996), it also recognizes oxidized phospholipids, such as oxidized PS and oxidized phosphatidylcholine, and may be functionally advantageous under oxidative stress (e.g., from intense light exposure) as an aid for the MERTK pathway (Greenberg et al., 2006; Sun et al., 2006).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Greenberg et al., 2006
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- Authors
- Greenberg, M. E., Sun, M., Zhang, R., Febbraio, M., Silverstein, R., & Hazen, S. L.
- Affiliations
- Cleveland Clinic (US)
- 1Department of Cell Biology
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-11-13
- Volume
- 203
- Issue
- 12
- Pages
- 2613-2625
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2118161
- OpenAlex
- W2134101952
- Cited by
- 430
- References
- 41
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 18 · 2023: 16 · 2022: 20 · 2021: 18 · 2020: 25 · 2019: 20 · 2018: 18 · 2017: 15 · 2016: 18 · 2015: 25 · 2014: 23 · 2013: 23 · 2012: 30
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Cleveland Clinic
- Cleveland Clinic Foundation
- National Institutes of Health (RR018390, HL076491)
- National Heart, Lung, and Blood Institute (P01 HL77107, HL61878, R01HL061878, P50HL077107, P01HL076491, HL 70621, R01HL070621)
- National Center for Research Resources (M01RR018390)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- efferocytosis, phagocytosis, macrophages, CD36, phosphatidylcholine oxidation, scavenger receptors, programmed cell death, apoptotic cell recognition, ligand-receptor interactions
- MeSH terms
- Animals, Cells, Cultured, Chlorocebus aethiops, Humans, Macrophages, Mice, Inbred C57BL, Oxidation-Reduction, Phagocytosis, Phosphatidylserines, Apoptosis, Mice, Knockout, HL-60 Cells, CD36 Antigens, Jurkat Cells, COS Cells, K562 Cells, Mice
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