Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes
Open accessAbstract
Phagocyte recognition, uptake, and nonphlogistic degradation of neutrophils and other leukocytes undergoing apoptosis promote the resolution of inflammation. This study assessed the effects of anti-inflammatory glucocorticoids on this leukocyte clearance mechanism. Pretreatment of “semimature” 5-day human monocyte-derived macrophages (Mφ) for 24 h with methylprednisolone, dexamethasone, and hydrocortisone, but not the nonglucocorticoid steroids aldosterone, estradiol, and progesterone, potentiated phagocytosis of apoptotic neutrophils. These effects were specific in that the potentiated phagocytosis of apoptotic neutrophils was completely blocked by the glucocorticoid receptor antagonist RU38486, and glucocorticoids did not promote 5-day Mφ ingestion of opsonized erythrocytes. Similar glucocorticoid-mediated potentiation was observed with 5-day Mφ uptake of alternative apoptotic “targets” (eosinophils and Jurkat T cells) and in uptake of apoptotic neutrophils by alternative phagocytes (human glomerular mesangial cells and murine Mφ elicited into the peritoneum or derived from bone marrow). Importantly, methylprednisolone-mediated enhancement of the uptake of apoptotic neutrophils did not trigger the release of the chemokines IL-8 and monocyte chemoattractant protein-1. Furthermore, longer-term potentiation by methylprednisolone was observed in maturing human monocyte-derived Mφ, with greater increases in 5-day Mφ uptake of apoptotic cells being observed the earlier glucocorticoids were added during monocyte maturation into Mφ. We conclude that potentiation of nonphlogistic clearance of apoptotic leukocytes by phagocytes is a hitherto unrecognized property of glucocorticoids that has potential implications for therapies aimed at promoting the resolution of inflammatory diseases.
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Glucocorticoids promote antiinflammatory macrophage populations.
“glucocorticoids have been shown to promote antiinflammatory macrophage populations (70).”
From An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice (2011) · cites this paper as [70]
The Abstract and Discussion report that glucocorticoids increase macrophage uptake of apoptotic leukocytes, a noninflammatory activity that may help resolve inflammation. They do not establish that glucocorticoids promote distinct antiinflammatory macrophage populations; the demonstrated effect is on phagocytic function. (LLM, conf=0.84)
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“uptake of apoptotic neutrophils (22), possibly by alter-”
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“Among many agonists, glucocorticoids apparently promote anti-inflammatory macrophage populations [153].”
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- Authors
- Liu, Y., Cousin, J. M., Hughes, J., Van Damme, J., Seckl, J. R., Haslett, C., Dransfield, I., Savill, J., & Rossi, A. G.
- Affiliations
- University of Nottingham (GB)
- University of Edinburgh (GB)
- Katholieke Universiteit Leuven, Rega Institute , Leuven ,
- Western General Hospital (GB)
- Corresponding author
- Liu, Yuqing
- Hughes, Jeremy
- Savill, John
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-03
- Volume
- 162
- Issue
- 6
- Pages
- 3639-3646
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1906626576
- Cited by
- 299
- References
- 48
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 8 · 2020: 6 · 2019: 14 · 2018: 9 · 2017: 6 · 2016: 11 · 2015: 7 · 2014: 12 · 2013: 17 · 2012: 8
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (047273)
- University of Nottingham
- University of Edinburgh
- Medical Research Council (047273)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- glucocorticoids, efferocytosis, apoptotic neutrophils, monocyte-derived macrophages, methylprednisolone, dexamethasone, cortisol, glucocorticoid receptor, inflammation resolution, monocyte maturation, chemokines, interleukin-8, MCP-1, mesangial cells, eosinophils, Jurkat cells
- MeSH terms
- Animals, Cell Differentiation, Cycloheximide, Female, Glucocorticoids, Humans, Inflammation, Leukocytes, Macrophages, Mice, Inbred BALB C, Models, Biological, Monocytes, Neutrophils, Phagocytosis, Receptors, Glucocorticoid, Cellular Senescence, Apoptosis, Jurkat Cells, Mice
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