title: CD73 Activity is Dispensable for the Polarization of M2 Macrophages.
abstract: The ectoenzyme CD73 catalyzes the hydrolysis of AMP, and is one of the most important producers of extracellular adenosine. On regulatory T cells, CD73 is necessary for immunosuppressive functions, and on Th17 cells CD73-generated adenosine exerts anti-inflammatory effects. However, the expression and function of CD73 in pro-inflammatory M1 and in immunosuppressive M2 macrophages is largely unknown. Here we show that CD73 expression and enzyme activity were induced in in vitro polarized pro-inflammatory human M(LPS+TNF) monocytes/macrophages, while CD73 was absent from immunosuppressive M(IL-4+M-CSF)-polarized macrophages. Inhibition of CD73 activity with the inhibitor AMPCP did not affect the polarization of human monocytes. In mice, CD73 was present on resident peritoneal macrophages. In striking contrast, elicited peritoneal macrophages remained CD73 negative regardless of their polarization towards either a pro-inflammatory M(LPS) or anti-inflammatory M(IL-4c) direction. Finally, the ability of peritoneal macrophages to polarize to pro- and anti-inflammatory cells was perfectly normal in CD73-deficient mice in vivo. These data indicate that, in contrast to other major leukocyte subpopulations, CD73 activity on macrophages does not play a major role in their polarization and that in mice host CD73 on any cell type is not required in vivo for peritoneal macrophage polarization towards either a pro- or an anti-inflammatory direction.
authors.affiliation: Medicity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Eichin
authors.affiliation: Medicity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Juha P
authors.initials: JP
authors.lastname: Laurila
authors.affiliation: Medicity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: Medicity Research Laboratory, University of Turku, Turku, Finland; Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000737:chemistry; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D010641:Phenotype
chemical_list: D016207:Cytokines; D058851:GPI-Linked Proteins; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D015847:Interleukin-4; D000244:Adenosine Diphosphate; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D015720:5'-Nucleotidase; C548241:NT5E protein, human; C548242:Nt5e protein, mouse; D000241:Adenosine