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Creative Commons Lizenz creative commons licence
Titel (primär) Danger signal extracellular calcium initiates differentiation of monocytes into SPP1/osteopontin-producing macrophages
Autor Murthy, S.; Karkossa, I.; Schmidt, C.; Hoffmann, A.; Hagemann, T.; Rothe, K.; Seifert, O.; Anderegg, U.; von Bergen, M.; Schubert, K.; Rossol, M.
Journal / Serie Cell Death & Disease
Erscheinungsjahr 2022
Department iDiv; MOLSYB
Band/Volume 13
Seite von art. 53
Sprache englisch
Topic T9 Healthy Planet
Supplements https://static-content.springer.com/esm/art%3A10.1038%2Fs41419-022-04507-3/MediaObjects/41419_2022_4507_MOESM2_ESM.pdf
https://static-content.springer.com/esm/art%3A10.1038%2Fs41419-022-04507-3/MediaObjects/41419_2022_4507_MOESM3_ESM.xlsx
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Abstract The danger signal extracellular calcium is pathophysiologically increased in the synovial fluid of patients with rheumatoid arthritis (RA). Calcium activates the NLRP3-inflammasome via the calcium-sensing receptor in monocytes/macrophages primed by lipopolysaccharide, and this effect is mediated by the uptake of calciprotein particles (CPPs) formed out of calcium, phosphate, and fetuin-A. Aim of the study was to unravel the influence of calcium on monocytes when the priming signal is not present. Monocytes were isolated from the blood of healthy controls and RA patients. Macrophages were characterized using scRNA-seq, DNA microarray, and proteomics. Imaging flow cytometry was utilized to study intracellular events. Here we show that extracellular calcium and CPPs lead to the differentiation of monocytes into calcium-macrophages when the priming signal is absent. Additional growth factors are not needed, and differentiation is triggered by calcium-dependent CPP-uptake, lysosomal alkalization due to CPP overload, and TFEB- and STAT3-dependent increased transcription of the lysosomal gene network. Calcium-macrophages have a needle-like shape, are characterized by excessive, constitutive SPP1/osteopontin production and a strong pro-inflammatory cytokine response. Calcium-macrophages differentiated out of RA monocytes show a stronger manifestation of this phenotype, suggesting the differentiation process might lead to the pro-inflammatory macrophage response seen in the RA synovial membrane.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=25636
Murthy, S., Karkossa, I., Schmidt, C., Hoffmann, A., Hagemann, T., Rothe, K., Seifert, O., Anderegg, U., von Bergen, M., Schubert, K., Rossol, M. (2022):
Danger signal extracellular calcium initiates differentiation of monocytes into SPP1/osteopontin-producing macrophages
Cell Death Dis. 13 , art. 53