A rat model of purine nucleoside phosphorylase deficiency
Purine nucleoside phosphorylase (NP; EC 2.4.2.1) deficiency is associated with selective T-cell dysfunction and normal B-cell immunity. In order to create an in vivo model of this immune deficiency, we administered 8-aminoguanosine to rats. This water-soluble nucleoside was rapidly converted by NP t...
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| Veröffentlicht in: | Immunology 1986-09, Vol.59 (1), p.63-67 |
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| creator | OSBORNE, W. R. A BARTON, R. W |
| description | Purine nucleoside phosphorylase (NP; EC 2.4.2.1) deficiency is associated with selective T-cell dysfunction and normal B-cell immunity. In order to create an in vivo model of this immune deficiency, we administered 8-aminoguanosine to rats. This water-soluble nucleoside was rapidly converted by NP to the more potent inhibitor 8-aminoguanine, which has a Ki of 0.19 microM. The accumulation of inosine in plasma showed that administration of 8-aminoguanosine was effectively inhibiting NP activity. The administration of 8-aminoguanosine with deoxyguanosine produced increased levels of dGTP only in thymus cells, and increased levels of GTP in cells from thymus, spleen and lymph node and in red cells. This correlated with assays of deoxyguanosine kinase, which showed significantly higher activity in thymus cells than in cells from spleen and lymph node. The intraperitoneal injection of 8-aminoguanosine alone or with deoxyguanosine for 8 consecutive days caused significant decreases in the number of thymus cells (P less than 0.001) and in lymph node and spleen lymphocytes (P less than 0.01). These data showed that the administration of 8-aminoguanosine to rats provided an animal model of NP deficiency that will allow studies of the specific regulation of T-cell function. |
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R. A ; BARTON, R. W</creator><creatorcontrib>OSBORNE, W. R. A ; BARTON, R. W</creatorcontrib><description>Purine nucleoside phosphorylase (NP; EC 2.4.2.1) deficiency is associated with selective T-cell dysfunction and normal B-cell immunity. In order to create an in vivo model of this immune deficiency, we administered 8-aminoguanosine to rats. This water-soluble nucleoside was rapidly converted by NP to the more potent inhibitor 8-aminoguanine, which has a Ki of 0.19 microM. The accumulation of inosine in plasma showed that administration of 8-aminoguanosine was effectively inhibiting NP activity. The administration of 8-aminoguanosine with deoxyguanosine produced increased levels of dGTP only in thymus cells, and increased levels of GTP in cells from thymus, spleen and lymph node and in red cells. This correlated with assays of deoxyguanosine kinase, which showed significantly higher activity in thymus cells than in cells from spleen and lymph node. The intraperitoneal injection of 8-aminoguanosine alone or with deoxyguanosine for 8 consecutive days caused significant decreases in the number of thymus cells (P less than 0.001) and in lymph node and spleen lymphocytes (P less than 0.01). These data showed that the administration of 8-aminoguanosine to rats provided an animal model of NP deficiency that will allow studies of the specific regulation of T-cell function.</description><identifier>ISSN: 0019-2805</identifier><identifier>EISSN: 1365-2567</identifier><identifier>PMID: 3019875</identifier><identifier>CODEN: IMMUAM</identifier><language>eng</language><publisher>Oxford: Blackwell</publisher><subject>Analysis of the immune response. Humoral and cellular immunity ; Animals ; Biological and medical sciences ; Deoxyguanine Nucleotides - metabolism ; Deoxyguanosine - blood ; Disease Models, Animal ; Erythrocytes - enzymology ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Guanosine - analogs & derivatives ; Guanosine - toxicity ; Guanosine Triphosphate - metabolism ; Immunobiology ; Lymphoid Tissue - metabolism ; Male ; Organs and cells involved in the immune response ; Pentosyltransferases - deficiency ; Phosphotransferases (Alcohol Group Acceptor) ; Phosphotransferases - metabolism ; Purine-Nucleoside Phosphorylase - antagonists & inhibitors ; Purine-Nucleoside Phosphorylase - deficiency ; Rats ; Rats, Inbred Lew</subject><ispartof>Immunology, 1986-09, Vol.59 (1), p.63-67</ispartof><rights>1987 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1453139/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1453139/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8042557$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3019875$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OSBORNE, W. R. A</creatorcontrib><creatorcontrib>BARTON, R. W</creatorcontrib><title>A rat model of purine nucleoside phosphorylase deficiency</title><title>Immunology</title><addtitle>Immunology</addtitle><description>Purine nucleoside phosphorylase (NP; EC 2.4.2.1) deficiency is associated with selective T-cell dysfunction and normal B-cell immunity. In order to create an in vivo model of this immune deficiency, we administered 8-aminoguanosine to rats. This water-soluble nucleoside was rapidly converted by NP to the more potent inhibitor 8-aminoguanine, which has a Ki of 0.19 microM. The accumulation of inosine in plasma showed that administration of 8-aminoguanosine was effectively inhibiting NP activity. The administration of 8-aminoguanosine with deoxyguanosine produced increased levels of dGTP only in thymus cells, and increased levels of GTP in cells from thymus, spleen and lymph node and in red cells. This correlated with assays of deoxyguanosine kinase, which showed significantly higher activity in thymus cells than in cells from spleen and lymph node. The intraperitoneal injection of 8-aminoguanosine alone or with deoxyguanosine for 8 consecutive days caused significant decreases in the number of thymus cells (P less than 0.001) and in lymph node and spleen lymphocytes (P less than 0.01). These data showed that the administration of 8-aminoguanosine to rats provided an animal model of NP deficiency that will allow studies of the specific regulation of T-cell function.</description><subject>Analysis of the immune response. Humoral and cellular immunity</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Deoxyguanine Nucleotides - metabolism</subject><subject>Deoxyguanosine - blood</subject><subject>Disease Models, Animal</subject><subject>Erythrocytes - enzymology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Guanosine - analogs & derivatives</subject><subject>Guanosine - toxicity</subject><subject>Guanosine Triphosphate - metabolism</subject><subject>Immunobiology</subject><subject>Lymphoid Tissue - metabolism</subject><subject>Male</subject><subject>Organs and cells involved in the immune response</subject><subject>Pentosyltransferases - deficiency</subject><subject>Phosphotransferases (Alcohol Group Acceptor)</subject><subject>Phosphotransferases - metabolism</subject><subject>Purine-Nucleoside Phosphorylase - antagonists & inhibitors</subject><subject>Purine-Nucleoside Phosphorylase - deficiency</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><issn>0019-2805</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1986</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1LxDAQhoMo67r6E4QcvBbynfQiLIu6woIXPZdsOnUjaVqSVui_t2BZ9DC8DM-8z2Eu0JpyJQsmlb5Ea0JoWTBD5DW6yflrXjmRcoVWfAZGyzUqtzjZAbddDQF3De7H5CPgOLoAXfY14P7U5XnSFGwGXEPjnYfoplt01diQ4W7JDfp4fnrf7YvD28vrbnsoelaSodBSEAbcak2hVk4TpuFogHHFtGBOgqDSUA6NY0xQowgVQIhWXHAFrjR8gx5_vf14bKF2EIdkQ9Un39o0VZ311X8S_an67L4rKiSnvJwF938F5-byg5k_LNxmZ0OTbHQ-n88MEUxKzX8A1KFlig</recordid><startdate>19860901</startdate><enddate>19860901</enddate><creator>OSBORNE, W. R. A</creator><creator>BARTON, R. W</creator><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>5PM</scope></search><sort><creationdate>19860901</creationdate><title>A rat model of purine nucleoside phosphorylase deficiency</title><author>OSBORNE, W. R. A ; BARTON, R. W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p290t-75402e3a771ed6c7027eb8e2362742c5e415813efc224186014e00763436ec983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Analysis of the immune response. Humoral and cellular immunity</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Deoxyguanine Nucleotides - metabolism</topic><topic>Deoxyguanosine - blood</topic><topic>Disease Models, Animal</topic><topic>Erythrocytes - enzymology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Guanosine - analogs & derivatives</topic><topic>Guanosine - toxicity</topic><topic>Guanosine Triphosphate - metabolism</topic><topic>Immunobiology</topic><topic>Lymphoid Tissue - metabolism</topic><topic>Male</topic><topic>Organs and cells involved in the immune response</topic><topic>Pentosyltransferases - deficiency</topic><topic>Phosphotransferases (Alcohol Group Acceptor)</topic><topic>Phosphotransferases - metabolism</topic><topic>Purine-Nucleoside Phosphorylase - antagonists & inhibitors</topic><topic>Purine-Nucleoside Phosphorylase - deficiency</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OSBORNE, W. R. A</creatorcontrib><creatorcontrib>BARTON, R. W</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OSBORNE, W. R. A</au><au>BARTON, R. W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A rat model of purine nucleoside phosphorylase deficiency</atitle><jtitle>Immunology</jtitle><addtitle>Immunology</addtitle><date>1986-09-01</date><risdate>1986</risdate><volume>59</volume><issue>1</issue><spage>63</spage><epage>67</epage><pages>63-67</pages><issn>0019-2805</issn><eissn>1365-2567</eissn><coden>IMMUAM</coden><abstract>Purine nucleoside phosphorylase (NP; EC 2.4.2.1) deficiency is associated with selective T-cell dysfunction and normal B-cell immunity. In order to create an in vivo model of this immune deficiency, we administered 8-aminoguanosine to rats. This water-soluble nucleoside was rapidly converted by NP to the more potent inhibitor 8-aminoguanine, which has a Ki of 0.19 microM. The accumulation of inosine in plasma showed that administration of 8-aminoguanosine was effectively inhibiting NP activity. The administration of 8-aminoguanosine with deoxyguanosine produced increased levels of dGTP only in thymus cells, and increased levels of GTP in cells from thymus, spleen and lymph node and in red cells. This correlated with assays of deoxyguanosine kinase, which showed significantly higher activity in thymus cells than in cells from spleen and lymph node. The intraperitoneal injection of 8-aminoguanosine alone or with deoxyguanosine for 8 consecutive days caused significant decreases in the number of thymus cells (P less than 0.001) and in lymph node and spleen lymphocytes (P less than 0.01). These data showed that the administration of 8-aminoguanosine to rats provided an animal model of NP deficiency that will allow studies of the specific regulation of T-cell function.</abstract><cop>Oxford</cop><pub>Blackwell</pub><pmid>3019875</pmid><tpages>5</tpages></addata></record> |
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| ispartof | Immunology, 1986-09, Vol.59 (1), p.63-67 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Analysis of the immune response. Humoral and cellular immunity Animals Biological and medical sciences Deoxyguanine Nucleotides - metabolism Deoxyguanosine - blood Disease Models, Animal Erythrocytes - enzymology Female Fundamental and applied biological sciences. Psychology Fundamental immunology Guanosine - analogs & derivatives Guanosine - toxicity Guanosine Triphosphate - metabolism Immunobiology Lymphoid Tissue - metabolism Male Organs and cells involved in the immune response Pentosyltransferases - deficiency Phosphotransferases (Alcohol Group Acceptor) Phosphotransferases - metabolism Purine-Nucleoside Phosphorylase - antagonists & inhibitors Purine-Nucleoside Phosphorylase - deficiency Rats Rats, Inbred Lew |
| title | A rat model of purine nucleoside phosphorylase deficiency |
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