title: Mesenchymal stem cells promote macrophage polarization toward M2b-like cells.
abstract: Mesenchymal stem or stromal cells (MSCs) act on different components of the immune response including macrophages (MΦs). Therefore this study has been committed to explore how MSCs may modify the effect of MΦ polarization upon an inductive environment using mouse bone marrow (BM)-derived "naïve", unpolarized MΦs. Phagocytosis of various MΦ subtypes was different since M1 and M2b showed poorer, while M2a higher rate of phagocytosis. MSCs significantly promoted yeast ingestion by M1 and M2b and diminished it by M2a cells. Under polarizing conditions, MSCs profoundly affected the TNFα production of MΦ subtypes since M1 and M2b MΦs produced less and M2a produced higher amount of TNFα while the amount of IL-10 was not affected. The most striking effect of MSCs was registered on M2b cells since the inflammatory TNFα dominance remarkably shifted to the immunosuppressive IL-10. Prepolarized M1 cells readily converted to M2a and M2b states when polarizing conditions changed from M1 to M2a or M2b induction, respectively. Repolarizing from M1 to M2a resulted in the decline of IL-10 and TNFα and defined elevation of Ym1 similar to levels characteristic to M2a primarily polarized from naïve BM-MΦs. Similarly, polarization of M1 to M2b MΦs was successful showing increase in IL-10 and reduction in TNFα levels characteristic to M2b cells. However, when co-culturing with MSCs, M1-M2a or M1-M2b transition was not affected. Crosstalk between MΦs and MSCs depended on PGE-2 since COX-2 inhibition reduced the effect of MSCs to establish an IL-10-dominant cytokine production by MΦs.
authors: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary; Stem Cell Biology Unit, National Blood Service, Budapest, Hungary.
authors: Gyöngyi
authors: G
authors: Kudlik
authors: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors: Beáta
authors: B
authors: Hegyi
authors: Institute of Genetics, Biological Research Center of Hungarian Academy of Sciences, Szeged, Hungary.
authors: Ágnes
authors: Á
authors: Czibula
authors: Institute of Genetics, Biological Research Center of Hungarian Academy of Sciences, Szeged, Hungary.
authors: Éva
authors: É
authors: Monostori
authors: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors: László
authors: L
authors: Buday
authors: Stem Cell Biology Unit, National Blood Service, Budapest, Hungary. Electronic address: uher.ferenc@gmail.com.
authors: Ferenc
authors: F
authors: Uher
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016764:Cell Polarity; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D012441:Saccharomyces cerevisiae / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015232:Dinoprostone
keywords: Bone marrow macrophages; M0, M1, M2a, and M2b macrophages; Mesenchymal stem cells; Peritoneal macrophages; Pro- and anti-inflammatory cytokines