Conversion of Acetaldehyde‐Protein Adduct Epitopes From a Nonreduced to a Reduced Phenotype by Antigen Processing Cells
Identifieur interne : 000716 ( Istex/Corpus ); précédent : 000715; suivant : 000717Conversion of Acetaldehyde‐Protein Adduct Epitopes From a Nonreduced to a Reduced Phenotype by Antigen Processing Cells
Auteurs : Lynell W. Klassen ; Bonnie L. Jones ; Michael F. Sorrell ; Dean J. Tuma ; Geoffrey M. ThieleSource :
- Alcoholism: Clinical and Experimental Research [ 0145-6008 ] ; 1999-04.
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Abstract
Many investigators have suggested that an immune reaction to acctaldchydc‐protein adducts may be involved in the development and/or progression of alcohol liver disease. The most often reported acetaldehyde adduct is the reduced adduct prepared in vitro in the presence of strong reducing agents. However, the production of this adduct in vivo has been difficult to prove. Nevertheless, the detection of scrum antibodies to this reduced adduct following alcohol exposure in animals and humans has been used to support the formation of this adduct in vivo. We have recently observed that when acetaldehyde‐protein adducts prepared under nonrcducing conditions are used to immunize animals, antibody to the reduced protein adduct is detected. Therefore, it was the purpose of this study to demonstrate that nonreduced (NR) adduct epitopes can be modified by intact cells to express reduced (R) adduct epitopes. This was accomplished using the monoclonal antibody RT1.1 that has been previously characterized by this laboratory and has been shown to recognize only R and not NR acetaldchyde adducts. In these studies, Balb/c mice were injected intraperitoneally (500 μg/animal) with either keyhole limpet hemocyanin (KLH)‐NR or KLH‐R adductcd proteins. Immunization with KLH‐NR produced significant amounts of antibodies that recognized both NR and R epitopes. In contrast, immunization with KLH‐R produced antibodies to only R and not NR epitopes. Isolated peritoneal macrophages from nonimmunized mice were incubated in vitro with either KLH‐NR, KLH‐R, or unmodified KLH proteins, and the cell surface expression of the reduced epitope (RT1.1) and the activated macrophage marker (MAC‐3) determined by double immunofluores‐cent staining. Activated macrophages incubated with KLH‐NR expressed the R adduct on 11.5% of the cells, compared with 3.8% following incubation with unmodified KLH, and 19.4% following incubation with KLH‐R. These data suggest that the NR adduct and/or the carrier protein are modified by peritoneal macrophages in vivo and present an epitope that is detected as a reduced adduct (RT1.1 positive). These observations may explain the presence of circulating antibodies to the reduced adduct that has been reported in human and animal studies.
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DOI: 10.1111/j.1530-0277.1999.tb04167.x
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Jones</name><affiliation><mods:affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</mods:affiliation></affiliation></author><author><name sortKey="Sorrell, Michael F" sort="Sorrell, Michael F" uniqKey="Sorrell M" first="Michael F." last="Sorrell">Michael F. 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Thiele</name><affiliation><mods:affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:F5678EC379164F95E17953F3FAE356B863174A47</idno><date when="1999" year="1999">1999</date><idno type="doi">10.1111/j.1530-0277.1999.tb04167.x</idno><idno type="url">https://api.istex.fr/document/F5678EC379164F95E17953F3FAE356B863174A47/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000716</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Conversion of Acetaldehyde‐Protein Adduct Epitopes From a Nonreduced to a Reduced Phenotype by Antigen Processing Cells</title><author><name sortKey="Klassen, Lynell W" sort="Klassen, Lynell W" uniqKey="Klassen L" first="Lynell W." last="Klassen">Lynell W. Klassen</name><affiliation><mods:affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</mods:affiliation></affiliation></author><author><name sortKey="Jones, Bonnie L" sort="Jones, Bonnie L" uniqKey="Jones B" first="Bonnie L" last="Jones">Bonnie L. Jones</name><affiliation><mods:affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</mods:affiliation></affiliation></author><author><name sortKey="Sorrell, Michael F" sort="Sorrell, Michael F" uniqKey="Sorrell M" first="Michael F." last="Sorrell">Michael F. Sorrell</name><affiliation><mods:affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</mods:affiliation></affiliation></author><author><name sortKey="Tuma, Dean J" sort="Tuma, Dean J" uniqKey="Tuma D" first="Dean J." last="Tuma">Dean J. Tuma</name><affiliation><mods:affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</mods:affiliation></affiliation></author><author><name sortKey="Thiele, Geoffrey M" sort="Thiele, Geoffrey M" uniqKey="Thiele G" first="Geoffrey M." last="Thiele">Geoffrey M. Thiele</name><affiliation><mods:affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Alcoholism: Clinical and Experimental Research</title><idno type="ISSN">0145-6008</idno><idno type="eISSN">1530-0277</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="1999-04">1999-04</date><biblScope unit="volume">23</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="657">657</biblScope><biblScope unit="page" to="663">663</biblScope></imprint><idno type="ISSN">0145-6008</idno></series><idno type="istex">F5678EC379164F95E17953F3FAE356B863174A47</idno><idno type="DOI">10.1111/j.1530-0277.1999.tb04167.x</idno><idno type="ArticleID">ACER657</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0145-6008</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetaldehyde</term><term>Alcohol</term><term>Antigen Processing Cells</term><term>Monoclonal Antibodies</term><term>Peritoneal Macrophages</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Many investigators have suggested that an immune reaction to acctaldchydc‐protein adducts may be involved in the development and/or progression of alcohol liver disease. The most often reported acetaldehyde adduct is the reduced adduct prepared in vitro in the presence of strong reducing agents. However, the production of this adduct in vivo has been difficult to prove. Nevertheless, the detection of scrum antibodies to this reduced adduct following alcohol exposure in animals and humans has been used to support the formation of this adduct in vivo. We have recently observed that when acetaldehyde‐protein adducts prepared under nonrcducing conditions are used to immunize animals, antibody to the reduced protein adduct is detected. Therefore, it was the purpose of this study to demonstrate that nonreduced (NR) adduct epitopes can be modified by intact cells to express reduced (R) adduct epitopes. This was accomplished using the monoclonal antibody RT1.1 that has been previously characterized by this laboratory and has been shown to recognize only R and not NR acetaldchyde adducts. In these studies, Balb/c mice were injected intraperitoneally (500 μg/animal) with either keyhole limpet hemocyanin (KLH)‐NR or KLH‐R adductcd proteins. Immunization with KLH‐NR produced significant amounts of antibodies that recognized both NR and R epitopes. In contrast, immunization with KLH‐R produced antibodies to only R and not NR epitopes. Isolated peritoneal macrophages from nonimmunized mice were incubated in vitro with either KLH‐NR, KLH‐R, or unmodified KLH proteins, and the cell surface expression of the reduced epitope (RT1.1) and the activated macrophage marker (MAC‐3) determined by double immunofluores‐cent staining. Activated macrophages incubated with KLH‐NR expressed the R adduct on 11.5% of the cells, compared with 3.8% following incubation with unmodified KLH, and 19.4% following incubation with KLH‐R. These data suggest that the NR adduct and/or the carrier protein are modified by peritoneal macrophages in vivo and present an epitope that is detected as a reduced adduct (RT1.1 positive). These observations may explain the presence of circulating antibodies to the reduced adduct that has been reported in human and animal studies.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Lynell W. Klassen</name><affiliations><json:string>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</json:string></affiliations></json:item><json:item><name>Bonnie L Jones</name><affiliations><json:string>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</json:string></affiliations></json:item><json:item><name>Michael F. Sorrell</name><affiliations><json:string>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</json:string></affiliations></json:item><json:item><name>Dean J. Tuma</name><affiliations><json:string>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</json:string></affiliations></json:item><json:item><name>Geoffrey M. Thiele</name><affiliations><json:string>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Alcohol</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Acetaldehyde</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Antigen Processing Cells</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Monoclonal Antibodies</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Peritoneal Macrophages</value></json:item></subject><articleId><json:string>ACER657</json:string></articleId><language><json:string>eng</json:string></language><abstract>Many investigators have suggested that an immune reaction to acctaldchydc‐protein adducts may be involved in the development and/or progression of alcohol liver disease. The most often reported acetaldehyde adduct is the reduced adduct prepared in vitro in the presence of strong reducing agents. However, the production of this adduct in vivo has been difficult to prove. Nevertheless, the detection of scrum antibodies to this reduced adduct following alcohol exposure in animals and humans has been used to support the formation of this adduct in vivo. We have recently observed that when acetaldehyde‐protein adducts prepared under nonrcducing conditions are used to immunize animals, antibody to the reduced protein adduct is detected. Therefore, it was the purpose of this study to demonstrate that nonreduced (NR) adduct epitopes can be modified by intact cells to express reduced (R) adduct epitopes. This was accomplished using the monoclonal antibody RT1.1 that has been previously characterized by this laboratory and has been shown to recognize only R and not NR acetaldchyde adducts. In these studies, Balb/c mice were injected intraperitoneally (500 μg/animal) with either keyhole limpet hemocyanin (KLH)‐NR or KLH‐R adductcd proteins. Immunization with KLH‐NR produced significant amounts of antibodies that recognized both NR and R epitopes. In contrast, immunization with KLH‐R produced antibodies to only R and not NR epitopes. Isolated peritoneal macrophages from nonimmunized mice were incubated in vitro with either KLH‐NR, KLH‐R, or unmodified KLH proteins, and the cell surface expression of the reduced epitope (RT1.1) and the activated macrophage marker (MAC‐3) determined by double immunofluores‐cent staining. Activated macrophages incubated with KLH‐NR expressed the R adduct on 11.5% of the cells, compared with 3.8% following incubation with unmodified KLH, and 19.4% following incubation with KLH‐R. These data suggest that the NR adduct and/or the carrier protein are modified by peritoneal macrophages in vivo and present an epitope that is detected as a reduced adduct (RT1.1 positive). These observations may explain the presence of circulating antibodies to the reduced adduct that has been reported in human and animal studies.</abstract><qualityIndicators><score>8.5</score><pdfVersion>1.4</pdfVersion><pdfPageSize>576 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>2264</abstractCharCount><pdfWordCount>5219</pdfWordCount><pdfCharCount>31222</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>335</abstractWordCount></qualityIndicators><title>Conversion of Acetaldehyde‐Protein Adduct Epitopes From a Nonreduced to a Reduced Phenotype by Antigen Processing Cells</title><genre><json:string>article</json:string></genre><host><volume>23</volume><publisherId><json:string>ACER</json:string></publisherId><pages><total>7</total><last>663</last><first>657</first></pages><issn><json:string>0145-6008</json:string></issn><issue>4</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1530-0277</json:string></eissn><title>Alcoholism: Clinical and Experimental Research</title><doi><json:string>10.1111/(ISSN)1530-0277</json:string></doi></host><publicationDate>1999</publicationDate><copyrightDate>1999</copyrightDate><doi><json:string>10.1111/j.1530-0277.1999.tb04167.x</json:string></doi><id>F5678EC379164F95E17953F3FAE356B863174A47</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/F5678EC379164F95E17953F3FAE356B863174A47/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/F5678EC379164F95E17953F3FAE356B863174A47/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/F5678EC379164F95E17953F3FAE356B863174A47/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Conversion of Acetaldehyde‐Protein Adduct Epitopes From a Nonreduced to a Reduced Phenotype by Antigen Processing Cells</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><availability><p>WILEY</p></availability><date>1999</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Conversion of Acetaldehyde‐Protein Adduct Epitopes From a Nonreduced to a Reduced Phenotype by Antigen Processing Cells</title><author><persName><forename type="first">Lynell W.</forename><surname>Klassen</surname></persName><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation></author><author><persName><forename type="first">Bonnie L</forename><surname>Jones</surname></persName><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation></author><author><persName><forename type="first">Michael F.</forename><surname>Sorrell</surname></persName><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation></author><author><persName><forename type="first">Dean J.</forename><surname>Tuma</surname></persName><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation></author><author><persName><forename type="first">Geoffrey M.</forename><surname>Thiele</surname></persName><note type="correspondence"><p>Correspondence: Reprint requests: Geoffrey M. Thiele, Ph.D., Omaha VA Medical Center, Research Service 151, Room 321, 4101 Woolworth Avenue, Omaha, NE 68105; Fax: (402)449‐0604; E‐mail:</p></note><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation></author></analytic><monogr><title level="j">Alcoholism: Clinical and Experimental Research</title><idno type="pISSN">0145-6008</idno><idno type="eISSN">1530-0277</idno><idno type="DOI">10.1111/(ISSN)1530-0277</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="1999-04"></date><biblScope unit="volume">23</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="657">657</biblScope><biblScope unit="page" to="663">663</biblScope></imprint></monogr><idno type="istex">F5678EC379164F95E17953F3FAE356B863174A47</idno><idno type="DOI">10.1111/j.1530-0277.1999.tb04167.x</idno><idno type="ArticleID">ACER657</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1999</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Many investigators have suggested that an immune reaction to acctaldchydc‐protein adducts may be involved in the development and/or progression of alcohol liver disease. The most often reported acetaldehyde adduct is the reduced adduct prepared in vitro in the presence of strong reducing agents. However, the production of this adduct in vivo has been difficult to prove. Nevertheless, the detection of scrum antibodies to this reduced adduct following alcohol exposure in animals and humans has been used to support the formation of this adduct in vivo. We have recently observed that when acetaldehyde‐protein adducts prepared under nonrcducing conditions are used to immunize animals, antibody to the reduced protein adduct is detected. Therefore, it was the purpose of this study to demonstrate that nonreduced (NR) adduct epitopes can be modified by intact cells to express reduced (R) adduct epitopes. This was accomplished using the monoclonal antibody RT1.1 that has been previously characterized by this laboratory and has been shown to recognize only R and not NR acetaldchyde adducts. In these studies, Balb/c mice were injected intraperitoneally (500 μg/animal) with either keyhole limpet hemocyanin (KLH)‐NR or KLH‐R adductcd proteins. Immunization with KLH‐NR produced significant amounts of antibodies that recognized both NR and R epitopes. In contrast, immunization with KLH‐R produced antibodies to only R and not NR epitopes. Isolated peritoneal macrophages from nonimmunized mice were incubated in vitro with either KLH‐NR, KLH‐R, or unmodified KLH proteins, and the cell surface expression of the reduced epitope (RT1.1) and the activated macrophage marker (MAC‐3) determined by double immunofluores‐cent staining. Activated macrophages incubated with KLH‐NR expressed the R adduct on 11.5% of the cells, compared with 3.8% following incubation with unmodified KLH, and 19.4% following incubation with KLH‐R. These data suggest that the NR adduct and/or the carrier protein are modified by peritoneal macrophages in vivo and present an epitope that is detected as a reduced adduct (RT1.1 positive). These observations may explain the presence of circulating antibodies to the reduced adduct that has been reported in human and animal studies.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Alcohol</term></item><item><term>Acetaldehyde</term></item><item><term>Antigen Processing Cells</term></item><item><term>Monoclonal Antibodies</term></item><item><term>Peritoneal Macrophages</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1999-04">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/F5678EC379164F95E17953F3FAE356B863174A47/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1530-0277</doi><issn type="print">0145-6008</issn><issn type="electronic">1530-0277</issn><idGroup><id type="product" value="ACER"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="ALCOHOLISM CLINICAL EXPERIMENTAL RESEARCH">Alcoholism: Clinical and Experimental Research</title></titleGroup></publicationMeta><publicationMeta level="part" position="04004"><doi origin="wiley">10.1111/acer.1999.23.issue-4</doi><numberingGroup><numbering type="journalVolume" number="23">23</numbering><numbering type="journalIssue" number="4">4</numbering></numberingGroup><coverDate startDate="1999-04">April 1999</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="0065700" status="forIssue"><doi origin="wiley">10.1111/j.1530-0277.1999.tb04167.x</doi><idGroup><id type="unit" value="ACER657"></id></idGroup><countGroup><count type="pageTotal" number="7"></count></countGroup><eventGroup><event type="firstOnline" date="2006-05-30"></event><event type="publishedOnlineFinalForm" date="2006-05-30"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.5 mode:FullText source:HeaderRef result:HeaderRef" date="2010-04-07"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2013-12-31"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="657">657</numbering><numbering type="pageLast" number="663">663</numbering></numberingGroup><correspondenceTo>Reprint requests: Geoffrey M. Thiele, Ph.D., Omaha VA Medical Center, Research Service 151, Room 321, 4101 Woolworth Avenue, Omaha, NE 68105; Fax: (402)449‐0604; E‐mail: <email>lthiele@juno.com.</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ACER.ACER657.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received for publication January 21, 1998; accepted February 3, 1999.</unparsedEditorialHistory><countGroup><count type="referenceTotal" number="39"></count><count type="linksCrossRef" number="6"></count></countGroup><titleGroup><title type="main">Conversion of Acetaldehyde‐Protein Adduct Epitopes From a Nonreduced to a Reduced Phenotype by Antigen Processing Cells</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>Lynell W.</givenNames><familyName>Klassen</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>Bonnie L</givenNames><familyName>Jones</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>Michael F.</givenNames><familyName>Sorrell</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a1"><personName><givenNames>Dean J.</givenNames><familyName>Tuma</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a1" corresponding="yes"><personName><givenNames>Geoffrey M.</givenNames><familyName>Thiele</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="US"><unparsedAffiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">Alcohol</keyword><keyword xml:id="k2">Acetaldehyde</keyword><keyword xml:id="k3">Antigen Processing Cells</keyword><keyword xml:id="k4">Monoclonal Antibodies</keyword><keyword xml:id="k5">Peritoneal Macrophages</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p>Many investigators have suggested that an immune reaction to acctaldchydc‐protein adducts may be involved in the development and/or progression of alcohol liver disease. The most often reported acetaldehyde adduct is the reduced adduct prepared in vitro in the presence of strong reducing agents. However, the production of this adduct in vivo has been difficult to prove. Nevertheless, the detection of scrum antibodies to this reduced adduct following alcohol exposure in animals and humans has been used to support the formation of this adduct in vivo. We have recently observed that when acetaldehyde‐protein adducts prepared under nonrcducing conditions are used to immunize animals, antibody to the reduced protein adduct is detected. Therefore, it was the purpose of this study to demonstrate that nonreduced (NR) adduct epitopes can be modified by intact cells to express reduced (R) adduct epitopes. This was accomplished using the monoclonal antibody RT1.1 that has been previously characterized by this laboratory and has been shown to recognize only R and not NR acetaldchyde adducts. In these studies, Balb/c mice were injected intraperitoneally (500 μg/animal) with either keyhole limpet hemocyanin (KLH)‐NR or KLH‐R adductcd proteins. Immunization with KLH‐NR produced significant amounts of antibodies that recognized both NR and R epitopes. In contrast, immunization with KLH‐R produced antibodies to only R and not NR epitopes. Isolated peritoneal macrophages from nonimmunized mice were incubated in vitro with either KLH‐NR, KLH‐R, or unmodified KLH proteins, and the cell surface expression of the reduced epitope (RT1.1) and the activated macrophage marker (MAC‐3) determined by double immunofluores‐cent staining. Activated macrophages incubated with KLH‐NR expressed the R adduct on 11.5% of the cells, compared with 3.8% following incubation with unmodified KLH, and 19.4% following incubation with KLH‐R. These data suggest that the NR adduct and/or the carrier protein are modified by peritoneal macrophages in vivo and present an epitope that is detected as a reduced adduct (RT1.1 positive). These observations may explain the presence of circulating antibodies to the reduced adduct that has been reported in human and animal studies.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="n-fnt-1" numbered="no"><p>This study was supported in part by the National Institute on Alcohol Abuse and Alcoholism (Grants ROIAA07818 and R01AA04961) and by the Department of Veterans Affairs Alcohol Research Center Grant awarded to the Omaha VA.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Conversion of Acetaldehyde‐Protein Adduct Epitopes From a Nonreduced to a Reduced Phenotype by Antigen Processing Cells</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Conversion of Acetaldehyde‐Protein Adduct Epitopes From a Nonreduced to a Reduced Phenotype by Antigen Processing Cells</title></titleInfo><name type="personal"><namePart type="given">Lynell W.</namePart><namePart type="family">Klassen</namePart><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bonnie L</namePart><namePart type="family">Jones</namePart><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael F.</namePart><namePart type="family">Sorrell</namePart><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dean J.</namePart><namePart type="family">Tuma</namePart><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Geoffrey M.</namePart><namePart type="family">Thiele</namePart><affiliation>Department of Veterans Affairs Alcohol Research Center (L.W.K., B.L.J., M.F.S., D.J.T., G.M.T.), Research Service, VA Medical Center; and University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology/Immunology (L.W.K., G.M.T.) and Section of Gastroenterology (M.F.S., D.J.T.), Omaha, Nebraska.</affiliation><description>Correspondence: Reprint requests: Geoffrey M. Thiele, Ph.D., Omaha VA Medical Center, Research Service 151, Room 321, 4101 Woolworth Avenue, Omaha, NE 68105; Fax: (402)449‐0604; E‐mail: </description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">1999-04</dateIssued><edition>Received for publication January 21, 1998; accepted February 3, 1999.</edition><copyrightDate encoding="w3cdtf">1999</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="references">39</extent></physicalDescription><abstract lang="en">Many investigators have suggested that an immune reaction to acctaldchydc‐protein adducts may be involved in the development and/or progression of alcohol liver disease. The most often reported acetaldehyde adduct is the reduced adduct prepared in vitro in the presence of strong reducing agents. However, the production of this adduct in vivo has been difficult to prove. Nevertheless, the detection of scrum antibodies to this reduced adduct following alcohol exposure in animals and humans has been used to support the formation of this adduct in vivo. We have recently observed that when acetaldehyde‐protein adducts prepared under nonrcducing conditions are used to immunize animals, antibody to the reduced protein adduct is detected. Therefore, it was the purpose of this study to demonstrate that nonreduced (NR) adduct epitopes can be modified by intact cells to express reduced (R) adduct epitopes. This was accomplished using the monoclonal antibody RT1.1 that has been previously characterized by this laboratory and has been shown to recognize only R and not NR acetaldchyde adducts. In these studies, Balb/c mice were injected intraperitoneally (500 μg/animal) with either keyhole limpet hemocyanin (KLH)‐NR or KLH‐R adductcd proteins. Immunization with KLH‐NR produced significant amounts of antibodies that recognized both NR and R epitopes. In contrast, immunization with KLH‐R produced antibodies to only R and not NR epitopes. Isolated peritoneal macrophages from nonimmunized mice were incubated in vitro with either KLH‐NR, KLH‐R, or unmodified KLH proteins, and the cell surface expression of the reduced epitope (RT1.1) and the activated macrophage marker (MAC‐3) determined by double immunofluores‐cent staining. Activated macrophages incubated with KLH‐NR expressed the R adduct on 11.5% of the cells, compared with 3.8% following incubation with unmodified KLH, and 19.4% following incubation with KLH‐R. These data suggest that the NR adduct and/or the carrier protein are modified by peritoneal macrophages in vivo and present an epitope that is detected as a reduced adduct (RT1.1 positive). These observations may explain the presence of circulating antibodies to the reduced adduct that has been reported in human and animal studies.</abstract><subject lang="en"><genre>Keywords</genre><topic>Alcohol</topic><topic>Acetaldehyde</topic><topic>Antigen Processing Cells</topic><topic>Monoclonal Antibodies</topic><topic>Peritoneal Macrophages</topic></subject><relatedItem type="host"><titleInfo><title>Alcoholism: Clinical and Experimental Research</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0145-6008</identifier><identifier type="eISSN">1530-0277</identifier><identifier type="DOI">10.1111/(ISSN)1530-0277</identifier><identifier type="PublisherID">ACER</identifier><part><date>1999</date><detail type="volume"><caption>vol.</caption><number>23</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>657</start><end>663</end><total>7</total></extent></part></relatedItem><identifier type="istex">F5678EC379164F95E17953F3FAE356B863174A47</identifier><identifier type="DOI">10.1111/j.1530-0277.1999.tb04167.x</identifier><identifier type="ArticleID">ACER657</identifier><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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