The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Regulation of Microglial Phagocytosis and Inflammatory Gene Expression by Gas6 Acting on the Axl/Mer Family of Tyrosine Kinases
Open accessAbstract
Removal of apoptotic cells is an essential process for normal development and tissue maintenance. Importantly, apoptotic cells stimulate their phagocytosis by macrophages while actively suppressing inflammatory responses. Growth arrest specific gene 6 (Gas6) is involved in this process, bridging phosphatidylserine residues on the surface of apoptotic cells to the Axl/Mer family of tyrosine kinases which stimulate phagocytosis. Animals with mutations or loss of these receptors exhibit phenotypes reflective of impaired phagocytosis and a hyperactive immune response. We report that Gas6 induces phagocytosis in microglia through a novel non-classical phagocytic mechanism. Gas6 stimulates a type-II-related phagocytic response, but requires Vav phosphorylation and Rac activation, distinguishing it from the classical type II mechanism. Importantly, Gas6 suppressed lipopolysaccharide-induced expression of the inflammatory molecules IL-1beta and iNOS. Gas6 inhibited iNOS expression through suppression of promoter activity. The present data provide direct evidence for the role of Gas6 receptors in mediating an anti-inflammatory response to ligands found on apoptotic cells with the simultaneous stimulation of phagocytosis. These data provide a mechanistic explanation for the phenotype observed in animals lacking Axl/Mer receptors.
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“We found that the expression of phagocytosis-related genes, including FCER1G, FCGR2A, TYROBP, and GAS6 (46–48), was down-regulated in AD monocytes as compared to AC monocytes (Fig. 3C), indicating a reduced ability of AD monocytes to phagocytose Aβ.”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [48]
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Metadata
- Authors
- Grommes, C., Lee, C. Y. D., Wilkinson, B. L., Jiang, Q., Koenigsknecht-Talboo, J. L., Varnum, B., & Landreth, G. E.
- Affiliations
- Case Western Reserve University (US)
- Washington University in St. Louis (US)
- Amgen (United States) (US)
- Corresponding author
- Landreth, Gary E.
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2007-10-10
- Volume
- 3
- Issue
- 2
- Pages
- 130-140
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- PMC
- PMC3653274
- OpenAlex
- W2161966903
- Cited by
- 162
- References
- 56
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 13 · 2023: 7 · 2022: 11 · 2021: 14 · 2020: 11 · 2019: 8 · 2018: 5 · 2017: 12 · 2016: 9 · 2015: 5 · 2014: 10 · 2013: 8 · 2012: 9
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Rockefeller Foundation
- National Institute on Aging (AG-20202, R01AG020202, R01AG016740, AG-16740)
- 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
- Gas6, microglial phagocytosis, efferocytosis, Rac activation, anti-inflammatory response, IL-1β, inducible nitric oxide synthase, lipopolysaccharide, inflammatory gene expression, phosphatidylserine
- MeSH terms
- c-Mer Tyrosine Kinase, Axl Receptor Tyrosine Kinase, Animals, Brain, Cell Line, Cytoskeleton, Gene Expression Regulation, Inflammation, Lipopolysaccharides, Phagocytosis, Phosphorylation, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Transcription, Genetic, Oncogene Proteins, Apoptosis, Microglia, rac GTP-Binding Proteins, Receptor Protein-Tyrosine Kinases, Intercellular Signaling Peptides and Proteins, Mice, Proto-Oncogene Proteins c-vav, Nitric Oxide Synthase Type II, Interleukin-1beta
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