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The mannose 6-phosphate/insulin-like growth factor 2 receptor mediates plasminogen-induced efferocytosis
A. Ohradanova-Repic, C. Machacek, C. Donner, V. Mühlgrabner, E. Petrovčíková, A. Zahradníková, K. Vičíková, V. Hořejší, H. Stockinger, V. Leksa,
Journal of leukocyte biology.
2019 ;
105 (3) :
519-530.
[pub] 20190118
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Perzistentní odkaz
https://www.medvik.cz/link/bmc19045041
- MeSH
- buněčná diferenciace účinky léků MeSH
- fagocytóza účinky léků MeSH
- fibroblasty účinky léků metabolismus MeSH
- genový knockout MeSH
- Jurkat buňky MeSH
- lidé MeSH
- makrofágy cytologie účinky léků metabolismus MeSH
- myši MeSH
- plazminogen farmakologie MeSH
- receptor IGF typ 2 metabolismus MeSH
- THP-1 buňky MeSH
- TNF-alfa metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The plasminogen system is harnessed in a wide variety of physiological processes, such as fibrinolysis, cell migration, or efferocytosis; and accordingly, it is essential upon inflammation, tissue remodeling, wound healing, and for homeostatic maintenance in general. Previously, we identified a plasminogen receptor in the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R, CD222). Here, we demonstrate by means of genetic knockdown, knockout, and rescue approaches combined with functional studies that M6P/IGF2R is up-regulated on the surface of macrophages, recognizes plasminogen exposed on the surface of apoptotic cells, and mediates plasminogen-induced efferocytosis. The level of uptake of plasminogen-coated apoptotic cells inversely correlates with the TNF-α production by phagocytes indicating tissue clearance without inflammation by this mechanism. Our results reveal an up-to-now undetermined function of M6P/IGF2R in clearance of apoptotic cells, which is crucial for tissue homeostasis.
Citace poskytuje Crossref.org
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