Immunization with the C-Terminal Region of Trypanosoma cruzi Ribosomal P1 and P2 Proteins Induces Long-Term Duration Cross-Reactive Antibodies with Heart Functional and Structural Alterations in Young and Aged Mice
The R13 peptide sequence (EEEDDDMGFGLFD) that corresponds to the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins differs from the eukariotic P concensus sequence EESDDDMGFGLFD (H13) only in a nonconservative amino acid substitution. The immunization of BALB/c mice with R13 synthe...
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description | The R13 peptide sequence (EEEDDDMGFGLFD) that corresponds to the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins differs from the eukariotic P concensus sequence EESDDDMGFGLFD (H13) only in a nonconservative amino acid substitution. The immunization of BALB/c mice with R13 synthetic peptide coupled to a carrier protein (OVA) induces specific (anti-R13) and autoreactive (anti-H13 and anti-heart) antibodies as well as heart functional alterations. Since aged human and experimental animals are impaired in their responses to most foreign antigens but they produce greater amounts of autoantibodies, in this work we used aged mice as an experimental model able to exaggerate the autoimmune component of the R13-induced response in case it was present. We studied whether these antibodies generated in the absence of the parasite would induce pathological changes in heart tissues. The levels of antibodies against R13 (foreign antigen) and H13 (autoantigen) studied comparatively in 2- and 12-month-old mice 10 days after the third immunization with R13 coupled to OVA were, as we expected for a foreign antigen, higher in almost all sera from 2-month-old mice tested than in sera from 12-month-old mice. Besides, these specific and cross-reactive antibody response remain elevated as long as 150 days post third immunization. In addition, the isotype pattern that recognizes R13 and the self-sequence H13 showed no differences between sera from young and aged mice. Moreover, when ECG traces were obtained from immunized mice, the heart functional alterations observed at 10 days continued at 80 and 150 days after the third immunization, showing an association with the levels of antibodies. In addition, despite the fact that the heart tissue morphology showed no alterations 10 days post third immunization, several abnormalities in the tissue architecture were revealed at 80 and 150 days post third immunization. This report demonstrates the biological relevance of R13-induced cross-reactive antibodies in some of the electrophysiologic and histological changes found in T. cruzi-infected mammalians. |
doi_str_mv | 10.1006/clim.2000.4919 |
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The immunization of BALB/c mice with R13 synthetic peptide coupled to a carrier protein (OVA) induces specific (anti-R13) and autoreactive (anti-H13 and anti-heart) antibodies as well as heart functional alterations. Since aged human and experimental animals are impaired in their responses to most foreign antigens but they produce greater amounts of autoantibodies, in this work we used aged mice as an experimental model able to exaggerate the autoimmune component of the R13-induced response in case it was present. We studied whether these antibodies generated in the absence of the parasite would induce pathological changes in heart tissues. The levels of antibodies against R13 (foreign antigen) and H13 (autoantigen) studied comparatively in 2- and 12-month-old mice 10 days after the third immunization with R13 coupled to OVA were, as we expected for a foreign antigen, higher in almost all sera from 2-month-old mice tested than in sera from 12-month-old mice. Besides, these specific and cross-reactive antibody response remain elevated as long as 150 days post third immunization. In addition, the isotype pattern that recognizes R13 and the self-sequence H13 showed no differences between sera from young and aged mice. Moreover, when ECG traces were obtained from immunized mice, the heart functional alterations observed at 10 days continued at 80 and 150 days after the third immunization, showing an association with the levels of antibodies. In addition, despite the fact that the heart tissue morphology showed no alterations 10 days post third immunization, several abnormalities in the tissue architecture were revealed at 80 and 150 days post third immunization. This report demonstrates the biological relevance of R13-induced cross-reactive antibodies in some of the electrophysiologic and histological changes found in T. cruzi-infected mammalians.</description><identifier>ISSN: 1521-6616</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1006/clim.2000.4919</identifier><identifier>PMID: 11027448</identifier><identifier>CODEN: CLIIFY</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Aging - physiology ; Animals ; Antibodies, Protozoan - immunology ; Biological and medical sciences ; Cross Reactions - immunology ; Female ; Heart - physiology ; Human protozoal diseases ; Infectious diseases ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Myocardium - pathology ; Parasitic diseases ; Protozoal diseases ; Protozoan Proteins - immunology ; ribosomal P1 protein ; ribosomal P2 protein ; ribosomal protein P1 ; ribosomal protein P2 ; Ribosomal Proteins - immunology ; Trypanosoma cruzi ; Trypanosomiasis</subject><ispartof>Clinical immunology (Orlando, Fla.), 2000-11, Vol.97 (2), p.89-94</ispartof><rights>2000 Academic Press</rights><rights>2001 INIST-CNRS</rights><rights>Copyright 2000 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-928f7566339ef92190a938cbccda693d05946345bfd4c53b0015c4553dfa075a3</citedby><cites>FETCH-LOGICAL-c400t-928f7566339ef92190a938cbccda693d05946345bfd4c53b0015c4553dfa075a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/clim.2000.4919$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1010294$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11027448$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Motrán, Claudia C.</creatorcontrib><creatorcontrib>Fretes, Ricardo E.</creatorcontrib><creatorcontrib>Cerbán, Fabio M.</creatorcontrib><creatorcontrib>Rivarola, Hector W.</creatorcontrib><creatorcontrib>Vottero de Cima, Elsa</creatorcontrib><title>Immunization with the C-Terminal Region of Trypanosoma cruzi Ribosomal P1 and P2 Proteins Induces Long-Term Duration Cross-Reactive Antibodies with Heart Functional and Structural Alterations in Young and Aged Mice</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>The R13 peptide sequence (EEEDDDMGFGLFD) that corresponds to the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins differs from the eukariotic P concensus sequence EESDDDMGFGLFD (H13) only in a nonconservative amino acid substitution. The immunization of BALB/c mice with R13 synthetic peptide coupled to a carrier protein (OVA) induces specific (anti-R13) and autoreactive (anti-H13 and anti-heart) antibodies as well as heart functional alterations. Since aged human and experimental animals are impaired in their responses to most foreign antigens but they produce greater amounts of autoantibodies, in this work we used aged mice as an experimental model able to exaggerate the autoimmune component of the R13-induced response in case it was present. We studied whether these antibodies generated in the absence of the parasite would induce pathological changes in heart tissues. The levels of antibodies against R13 (foreign antigen) and H13 (autoantigen) studied comparatively in 2- and 12-month-old mice 10 days after the third immunization with R13 coupled to OVA were, as we expected for a foreign antigen, higher in almost all sera from 2-month-old mice tested than in sera from 12-month-old mice. Besides, these specific and cross-reactive antibody response remain elevated as long as 150 days post third immunization. In addition, the isotype pattern that recognizes R13 and the self-sequence H13 showed no differences between sera from young and aged mice. Moreover, when ECG traces were obtained from immunized mice, the heart functional alterations observed at 10 days continued at 80 and 150 days after the third immunization, showing an association with the levels of antibodies. In addition, despite the fact that the heart tissue morphology showed no alterations 10 days post third immunization, several abnormalities in the tissue architecture were revealed at 80 and 150 days post third immunization. This report demonstrates the biological relevance of R13-induced cross-reactive antibodies in some of the electrophysiologic and histological changes found in T. cruzi-infected mammalians.</description><subject>Aging - physiology</subject><subject>Animals</subject><subject>Antibodies, Protozoan - immunology</subject><subject>Biological and medical sciences</subject><subject>Cross Reactions - immunology</subject><subject>Female</subject><subject>Heart - physiology</subject><subject>Human protozoal diseases</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Myocardium - pathology</subject><subject>Parasitic diseases</subject><subject>Protozoal diseases</subject><subject>Protozoan Proteins - immunology</subject><subject>ribosomal P1 protein</subject><subject>ribosomal P2 protein</subject><subject>ribosomal protein P1</subject><subject>ribosomal protein P2</subject><subject>Ribosomal Proteins - immunology</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosomiasis</subject><issn>1521-6616</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGO0zAQhiMEYpeFK0fkA-KWYsdxUh-rLstWKqIq5cDJcuxJ1yixi-0s2n1QngeniQQXxMm25vM3o_mz7DXBC4Jx9V51pl8UGONFyQl_kl0SVpC8xpQ9ne9VRaqL7EUI3xPFiqJ6nl0Qgou6LJeX2a9N3w_WPMponEU_TbxD8Q7QOj-A742VHdrDcSy5Fh38w0laF1wvkfLDo0F705yfHdoRJK1GuwLtvItgbEAbqwcFAW2dPZ516HrwU5-1dyHke5AqmntAKxuTSJsEnye4BekjuhmsGulkH9Vfoh9UTIYOrboIkykgY9E3N9jjmVkdQaNPRsHL7FkruwCv5vMq-3rz4bC-zbefP27Wq22uSoxjzotlW7OqopRDywvCseR0qRqltKw41ZjxsqIla1pdKkYbjAlTJWNUtxLXTNKr7N3kPXn3Y4AQRW-Cgq6TFtwQRF3QYok5-S9I6pQHIzSBiwlU4448tOLkTS_9gyBYjJGLMXIxRi7GyNOHN7N5aHrQf_A54wS8nQEZlOxaL60y4S9tAnmZsOWEQdrXvQEvgjJgFWjjQUWhnfnXCL8Bc1TKKA</recordid><startdate>20001101</startdate><enddate>20001101</enddate><creator>Motrán, Claudia C.</creator><creator>Fretes, Ricardo E.</creator><creator>Cerbán, Fabio M.</creator><creator>Rivarola, Hector W.</creator><creator>Vottero de Cima, Elsa</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>20001101</creationdate><title>Immunization with the C-Terminal Region of Trypanosoma cruzi Ribosomal P1 and P2 Proteins Induces Long-Term Duration Cross-Reactive Antibodies with Heart Functional and Structural Alterations in Young and Aged Mice</title><author>Motrán, Claudia C. ; Fretes, Ricardo E. ; Cerbán, Fabio M. ; Rivarola, Hector W. ; Vottero de Cima, Elsa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-928f7566339ef92190a938cbccda693d05946345bfd4c53b0015c4553dfa075a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Aging - physiology</topic><topic>Animals</topic><topic>Antibodies, Protozoan - immunology</topic><topic>Biological and medical sciences</topic><topic>Cross Reactions - immunology</topic><topic>Female</topic><topic>Heart - physiology</topic><topic>Human protozoal diseases</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Myocardium - pathology</topic><topic>Parasitic diseases</topic><topic>Protozoal diseases</topic><topic>Protozoan Proteins - immunology</topic><topic>ribosomal P1 protein</topic><topic>ribosomal P2 protein</topic><topic>ribosomal protein P1</topic><topic>ribosomal protein P2</topic><topic>Ribosomal Proteins - immunology</topic><topic>Trypanosoma cruzi</topic><topic>Trypanosomiasis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Motrán, Claudia C.</creatorcontrib><creatorcontrib>Fretes, Ricardo E.</creatorcontrib><creatorcontrib>Cerbán, Fabio M.</creatorcontrib><creatorcontrib>Rivarola, Hector W.</creatorcontrib><creatorcontrib>Vottero de Cima, Elsa</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>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical immunology (Orlando, Fla.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Motrán, Claudia C.</au><au>Fretes, Ricardo E.</au><au>Cerbán, Fabio M.</au><au>Rivarola, Hector W.</au><au>Vottero de Cima, Elsa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunization with the C-Terminal Region of Trypanosoma cruzi Ribosomal P1 and P2 Proteins Induces Long-Term Duration Cross-Reactive Antibodies with Heart Functional and Structural Alterations in Young and Aged Mice</atitle><jtitle>Clinical immunology (Orlando, Fla.)</jtitle><addtitle>Clin Immunol</addtitle><date>2000-11-01</date><risdate>2000</risdate><volume>97</volume><issue>2</issue><spage>89</spage><epage>94</epage><pages>89-94</pages><issn>1521-6616</issn><eissn>1521-7035</eissn><coden>CLIIFY</coden><abstract>The R13 peptide sequence (EEEDDDMGFGLFD) that corresponds to the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins differs from the eukariotic P concensus sequence EESDDDMGFGLFD (H13) only in a nonconservative amino acid substitution. The immunization of BALB/c mice with R13 synthetic peptide coupled to a carrier protein (OVA) induces specific (anti-R13) and autoreactive (anti-H13 and anti-heart) antibodies as well as heart functional alterations. Since aged human and experimental animals are impaired in their responses to most foreign antigens but they produce greater amounts of autoantibodies, in this work we used aged mice as an experimental model able to exaggerate the autoimmune component of the R13-induced response in case it was present. We studied whether these antibodies generated in the absence of the parasite would induce pathological changes in heart tissues. The levels of antibodies against R13 (foreign antigen) and H13 (autoantigen) studied comparatively in 2- and 12-month-old mice 10 days after the third immunization with R13 coupled to OVA were, as we expected for a foreign antigen, higher in almost all sera from 2-month-old mice tested than in sera from 12-month-old mice. Besides, these specific and cross-reactive antibody response remain elevated as long as 150 days post third immunization. In addition, the isotype pattern that recognizes R13 and the self-sequence H13 showed no differences between sera from young and aged mice. Moreover, when ECG traces were obtained from immunized mice, the heart functional alterations observed at 10 days continued at 80 and 150 days after the third immunization, showing an association with the levels of antibodies. In addition, despite the fact that the heart tissue morphology showed no alterations 10 days post third immunization, several abnormalities in the tissue architecture were revealed at 80 and 150 days post third immunization. This report demonstrates the biological relevance of R13-induced cross-reactive antibodies in some of the electrophysiologic and histological changes found in T. cruzi-infected mammalians.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>11027448</pmid><doi>10.1006/clim.2000.4919</doi><tpages>6</tpages></addata></record> |
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subjects | Aging - physiology Animals Antibodies, Protozoan - immunology Biological and medical sciences Cross Reactions - immunology Female Heart - physiology Human protozoal diseases Infectious diseases Medical sciences Mice Mice, Inbred BALB C Myocardium - pathology Parasitic diseases Protozoal diseases Protozoan Proteins - immunology ribosomal P1 protein ribosomal P2 protein ribosomal protein P1 ribosomal protein P2 Ribosomal Proteins - immunology Trypanosoma cruzi Trypanosomiasis |
title | Immunization with the C-Terminal Region of Trypanosoma cruzi Ribosomal P1 and P2 Proteins Induces Long-Term Duration Cross-Reactive Antibodies with Heart Functional and Structural Alterations in Young and Aged Mice |
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