title: Consequences of the lack of CD73 and prostatic acid phosphatase in the lymphoid organs.
abstract: CD73, ecto-5'-nucleotidase, is the key enzyme catalyzing the conversion of extracellular AMP to adenosine that controls vascular permeability and immunosuppression. Also prostatic acid phosphatase (PAP) possesses ecto-5'-nucleotidase/AMPase activity and is present in leukocytes. However, its role related to immune system is unknown. Therefore, we analyzed enzymatic activities and leukocyte subtypes of CD73 and PAP knockouts and generated CD73/PAP double knockout mice to elucidate the contribution of CD73 and PAP to immunological parameters. Enzymatic assays confirmed the ability of recombinant human PAP to hydrolyze [(3)H]AMP, although at much lower rate than human CD73. Nevertheless, 5'-nucleotidase/AMPase activity in splenocytes and lymphocytes from PAP(-/-) mice tended to be lower than in wild-type controls, suggesting potential contribution of PAP, along with CD73, into lymphoid AMP metabolism ex vivo. Single knockouts had decreased number of CD4(+)/CD25(+)/FoxP3 (+) regulatory T cells in thymus and CD73/PAP double knockouts exhibited reduced percentages of CD4(+) cells in spleen, regulatory T cells in lymph nodes and thymus, and CD4(+) and CD8(+) cells in blood. These findings suggest that PAP has a synergistic role together with CD73 in the immune system by contributing to the balance of leukocyte subpopulations and especially to the number of regulatory T cells in lymph nodes and thymus.
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland ; Department of Medical Microbiology and Immunology, University of Turku, 20014 Turku, Finland.
authors.forename: Gennady G
authors.initials: GG
authors.lastname: Yegutkin
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland ; National Institute for Health and Welfare, 20520 Turku, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Auvinen
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland.
authors.forename: Marika
authors.initials: M
authors.lastname: Karikoski
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland ; Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, 20014 Turku, Finland.
authors.forename: Pia
authors.identifier: 0000-0003-1638-5075
authors.initials: P
authors.lastname: Rantakari
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Gerke
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland ; Department of Medical Biochemistry and Genetics, University of Turku, 20014 Turku, Finland.
authors.forename: Kati
authors.initials: K
authors.lastname: Elima
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland.
authors.forename: Mikael
authors.identifier: 0000-0003-3433-700X
authors.initials: M
authors.lastname: Maksimow
authors.affiliation: Department of Clinical Chemistry, and Helsinki University Hospital Laboratory, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Ileana B
authors.initials: IB
authors.lastname: Quintero
authors.affiliation: Department of Clinical Chemistry, and Helsinki University Hospital Laboratory, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Vihko
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland ; Department of Medical Microbiology and Immunology, University of Turku, 20014 Turku, Finland ; National Institute for Health and Welfare, 20520 Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland ; Department of Medical Microbiology and Immunology, University of Turku, 20014 Turku, Finland ; National Institute for Health and Welfare, 20520 Turku, Finland.
authors.forename: Sirpa
authors.identifier: 0000-0002-1922-9732
authors.initials: S
authors.lastname: Jalkanen
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000135:Acid Phosphatase; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002855:Chromatography, Thin Layer; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases; D015720:5'-Nucleotidase