The pattern-recognition molecule mindin binds integrin Mac-1 to promote macrophage phagocytosis via Syk activation and NF-κB p65 translocation
Open accessAbstract
Mindin has a broad spectrum of roles in the innate immune system, including in macrophage migration, antigen phagocytosis and cytokine production. Mindin functions as a pattern‐recognition molecule for microbial pathogens. However, the underlying mechanisms of mindin‐mediated phagocytosis and its exact membrane receptors are not well established. Herein, we generated mindin‐deficient mice using the CRISPR‐Cas9 system and show that peritoneal macrophages from mindin‐deficient mice were severely defective in their ability to phagocytize E coli. Phagocytosis was enhanced when E coli or fluorescent particles were pre‐incubated with mindin, indicating that mindin binds directly to bacteria or non‐pathogen particles and promotes phagocytosis. We defined that 131 I‐labelled mindin binds with integrin Mac‐1 (CD11b/CD18), the F‐spondin (FS)‐fragment of mindin binds with the α M‐I domain of Mac‐1 and that mindin serves as a novel ligand of Mac‐1. Blockade of the α M‐I domain of Mac‐1 using either a neutralizing antibody or si‐Mac‐1 efficiently blocked mindin‐induced phagocytosis. Furthermore, mindin activated the Syk and MAPK signalling pathways and promoted NF‐κB entry into the nucleus. Our data indicate that mindin binds with the integrin Mac‐1 to promote macrophage phagocytosis through Syk activation and NF‐κB p65 translocation, suggesting that the mindin/Mac‐1 axis plays a critical role during innate immune responses.
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Other inflammation-related genes dysregulated in hEDS/HSD include SPON2 up-regulated and PRLR decreased.
“Other inflammation-related genes dysregulated in hEDS/HSD include SPON2, up-regulated in patients’ cells, which encodes an ECM protein with multifunctional properties in the innate immune system and inflammatory cell recruitment [152,153,154], and PRLR, showing a decreased expression in hEDS/HSD cells, which encode the prolactin receptor implicated in inflammatory responses and immune cells”
From Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes (2019) · cites this paper as [154]
SPON2 encodes an ECM protein with multifunctional properties in the innate immune system and inflammatory cell recruitment.
“Other inflammation-related genes dysregulated in hEDS/HSD include SPON2, up-regulated in patients’ cells, which encodes an ECM protein with multifunctional properties in the innate immune system and inflammatory cell recruitment [152,153,154], and PRLR, showing a decreased expression in hEDS/HSD cells, which encode the prolactin receptor implicated in inflammatory responses and immune cells”
From Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes (2019) · cites this paper as [154]
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- Authors
- Liu, Y., Wang, L., Cheng, X., Huo, Y., Ouyang, X., Liang, L., Lin, Y., Wu, J., Ren, J., & Guleng, B.
- Affiliations
- Xiamen University (CN)
- State Key Laboratory of Cellular Stress Biology, School of life sciences Xiamen University Xiamen China
- Department of Gastroenterology Zhongshan Hospital affiliated to Xiamen University Xiamen China
- Corresponding author
- Guleng, Bayasi
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2019-03-14
- Volume
- 23
- Issue
- 5
- Pages
- 3402-3416
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC6484411
- OpenAlex
- W2922066498
- Cited by
- 20
- References
- 41
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 2 · 2021: 6 · 2020: 4 · 2019: 2
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation (81770548, 81770558, 81570496)
- 973 programs (2015CB553800)
- National Clinical Research Center for Digestive Diseases, Xi'an (2015BAI13B07)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- mindin, Mac-1, CD11b/CD18, macrophage phagocytosis, pattern recognition molecules, Syk activation, p65 nuclear translocation, F-spondin, integrin ligands, innate immunity, Escherichia coli, MAPK signaling, CRISPR/Cas9 knockout mice
- MeSH terms
- RAW 264.7 Cells, Syk Kinase, Protein Domains, Animals, Base Sequence, Cell Nucleus, Humans, Macrophages, Phagocytosis, Phosphorylation, Protein Binding, Macrophage-1 Antigen, Extracellular Matrix Proteins, Mice, Knockout, Protein Transport, Receptors, Pattern Recognition, Mice, Transcription Factor RelA, HEK293 Cells
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