S100A8/A9 drives monocytes towards M2-like macrophage differentiation and associates with M2-like macrophages in osteoarthritic synovium.

Autor:	van Kooten NJT; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.; Orthopedics, Canisius Wilhelmina Ziekenhuis, Nijmegen, the Netherlands., Blom AB; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Teunissen van Manen IJ; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Theeuwes WF; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Roth J; Institute of Immunology, University of Münster, Münster, Germany., Gorris MAJ; Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.; Division of Immunotherapy, Oncode Institute, Radboudumc, Nijmegen, the Netherlands., Walgreen B; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Sloetjes AW; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Helsen MM; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Vitters EL, van Lent PLEM; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Koëter S; Orthopedics, Canisius Wilhelmina Ziekenhuis, Nijmegen, the Netherlands., van der Kraan PM; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Vogl T; Institute of Immunology, University of Münster, Münster, Germany., van den Bosch MHJ; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Jan 12. Date of Electronic Publication: 2024 Jan 12.
DOI:	10.1093/rheumatology/keae020
Abstrakt:	Objectives: Macrophages are key orchestrators of the osteoarthritis (OA)-associated inflammatory response. Macrophage phenotype is dependent on environmental cues like the inflammatory factor S100A8/A9. Here, we investigated how S100A9 exposure during monocyte-to-macrophage differentiation affects macrophage phenotype and function. Methods: OA synovium cellular composition was determined using flow cytometry and multiplex immunohistochemistry. Healthy donor monocytes were differentiated towards M1- and M2-like macrophages in presence of S100A9. Macrophage markers were measured using flow cytometry and phagocytic activity was determined using pHrodo Red Zymosan A BioParticles. Gene expression was determined using qPCR. Protein secretion was measured using Luminex and ELISA. Results: Macrophages were the dominant leucocyte subpopulation in OA synovium. They mainly presented with a M2-like phenotype, although the majority also expressed M1-like macrophage markers. Long-term exposure to S100A9 during monocyte-to-macrophage differentiation increased M2-like macrophage markers CD163 and CD206 in M1-like and M2-like differentiated cells. In addition, M1-like macrophage markers were increased in M1-like, but decreased in M2-like differentiated macrophages. In agreement with this mixed phenotype, S100A9 stimulation modestly increased expression and secretion of pro-inflammatory markers and catabolic enzymes, but also increased expression and secretion of anti-inflammatory/anabolic markers. In accordance with the upregulation of M2-like macrophage markers, S100A9 increased phagocytic activity. Finally, we indeed observed a strong association between S100A8 and S100A9 expression and the M2-like/M1-like macrophage ratio in end-stage OA synovium. Conclusion: Chronic S100A8/A9 exposure during monocyte-to-macrophage differentiation favours differentiation towards a M2-like macrophage phenotype. The properties of these cells could help explain the catabolic/anabolic dualism in established OA joints with low-grade inflammation. (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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