Consequences of the Lack of CD73 and Prostatic Acid Phosphatase in the Lymphoid Organs
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 re...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/485743 |
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| author | Gennady G. Yegutkin Kaisa Auvinen Marika Karikoski Pia Rantakari Heidi Gerke Kati Elima Mikael Maksimow Ileana B. Quintero Pirkko Vihko Marko Salmi Sirpa Jalkanen |
| author_facet | Gennady G. Yegutkin Kaisa Auvinen Marika Karikoski Pia Rantakari Heidi Gerke Kati Elima Mikael Maksimow Ileana B. Quintero Pirkko Vihko Marko Salmi Sirpa Jalkanen |
| author_sort | Gennady G. Yegutkin |
| collection | DOAJ |
| description | 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 [3H]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. |
| format | Article |
| id | doaj-art-26c6a64f5c944cc3a3f5370f6e65198f |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-26c6a64f5c944cc3a3f5370f6e65198f2025-02-03T06:12:56ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/485743485743Consequences of the Lack of CD73 and Prostatic Acid Phosphatase in the Lymphoid OrgansGennady G. Yegutkin0Kaisa Auvinen1Marika Karikoski2Pia Rantakari3Heidi Gerke4Kati Elima5Mikael Maksimow6Ileana B. Quintero7Pirkko Vihko8Marko Salmi9Sirpa Jalkanen10MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandDepartment of Clinical Chemistry, and Helsinki University Hospital Laboratory, University of Helsinki, 00014 Helsinki, FinlandDepartment of Clinical Chemistry, and Helsinki University Hospital Laboratory, University of Helsinki, 00014 Helsinki, FinlandMediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMediCity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandCD73, 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 [3H]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.http://dx.doi.org/10.1155/2014/485743 |
| spellingShingle | Gennady G. Yegutkin Kaisa Auvinen Marika Karikoski Pia Rantakari Heidi Gerke Kati Elima Mikael Maksimow Ileana B. Quintero Pirkko Vihko Marko Salmi Sirpa Jalkanen Consequences of the Lack of CD73 and Prostatic Acid Phosphatase in the Lymphoid Organs Mediators of Inflammation |
| title | Consequences of the Lack of CD73 and Prostatic Acid Phosphatase in the Lymphoid Organs |
| title_full | Consequences of the Lack of CD73 and Prostatic Acid Phosphatase in the Lymphoid Organs |
| title_fullStr | Consequences of the Lack of CD73 and Prostatic Acid Phosphatase in the Lymphoid Organs |
| title_full_unstemmed | Consequences of the Lack of CD73 and Prostatic Acid Phosphatase in the Lymphoid Organs |
| title_short | Consequences of the Lack of CD73 and Prostatic Acid Phosphatase in the Lymphoid Organs |
| title_sort | consequences of the lack of cd73 and prostatic acid phosphatase in the lymphoid organs |
| url | http://dx.doi.org/10.1155/2014/485743 |
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