A murine model of acute liver injury induced by human monoclonal autoantibody
We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hep...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2005-07, Vol.42 (1), p.149-155 |
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| creator | YAMAUCHI, Katsumi YAMAGUCHI, Naoko SHIRATORI, Keiko FURUKAWA, Takaji TAKATSU, Kazuko NAKANISHI, Toshimi ISHIDA, Kohji KOMATSU, Tatsuji TOKUSHIGE, Katsutoshi NAGAHARA, Hikaru HASHIMOTO, Etsuko |
| description | We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH. |
| doi_str_mv | 10.1002/hep.20726 |
| format | Article |
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This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH.</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.20726</identifier><identifier>PMID: 15918155</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Hoboken, NJ: Wiley</publisher><subject>Animals ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - immunology ; Autoantibodies - adverse effects ; Autoantibodies - immunology ; Biological and medical sciences ; Drug toxicity and drugs side effects treatment ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepatitis, Autoimmune - immunology ; Hepatocytes - immunology ; Hepatocytes - pathology ; Humans ; Immunoglobulin M - adverse effects ; Immunoglobulin M - immunology ; Liver Failure, Acute - immunology ; Liver. Bile. Biliary tracts ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Mice ; Models, Animal ; Necrosis ; Other diseases. Semiology ; Pharmacology. Drug treatments ; Toxicity: digestive system ; Vertebrates: digestive system</subject><ispartof>Hepatology (Baltimore, Md.), 2005-07, Vol.42 (1), p.149-155</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c313t-3d09d4189bd370f2d61646d774a26dc9f5d1acdbd083f0a51529d37997be80da3</citedby><cites>FETCH-LOGICAL-c313t-3d09d4189bd370f2d61646d774a26dc9f5d1acdbd083f0a51529d37997be80da3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16925516$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15918155$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>YAMAUCHI, Katsumi</creatorcontrib><creatorcontrib>YAMAGUCHI, Naoko</creatorcontrib><creatorcontrib>SHIRATORI, Keiko</creatorcontrib><creatorcontrib>FURUKAWA, Takaji</creatorcontrib><creatorcontrib>TAKATSU, Kazuko</creatorcontrib><creatorcontrib>NAKANISHI, Toshimi</creatorcontrib><creatorcontrib>ISHIDA, Kohji</creatorcontrib><creatorcontrib>KOMATSU, Tatsuji</creatorcontrib><creatorcontrib>TOKUSHIGE, Katsutoshi</creatorcontrib><creatorcontrib>NAGAHARA, Hikaru</creatorcontrib><creatorcontrib>HASHIMOTO, Etsuko</creatorcontrib><title>A murine model of acute liver injury induced by human monoclonal autoantibody</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Autoantibodies - adverse effects</subject><subject>Autoantibodies - immunology</subject><subject>Biological and medical sciences</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepatitis, Autoimmune - immunology</subject><subject>Hepatocytes - immunology</subject><subject>Hepatocytes - pathology</subject><subject>Humans</subject><subject>Immunoglobulin M - adverse effects</subject><subject>Immunoglobulin M - immunology</subject><subject>Liver Failure, Acute - immunology</subject><subject>Liver. Bile. Biliary tracts</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Models, Animal</subject><subject>Necrosis</subject><subject>Other diseases. Semiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Toxicity: digestive system</subject><subject>Vertebrates: digestive system</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0E9LwzAYx_EgipvTg29AclHw0PkkadLmOIb_YOJFzyVNUtbRNjNphL57ow52-l0-PPB8EbomsCQA9GFr90sKBRUnaE44LTLGOJyiOdACMkmYnKGLEHYAIHNanqMZ4ZKUhPM5elvhPvp2sLh3xnbYNVjpOFrctd_W43bYRT-lMVFbg-sJb2OvhoQHpzs3qA6rODo1jG3tzHSJzhrVBXt12AX6fHr8WL9km_fn1_Vqk2lG2JgxA9LkpJS1YQU01AgicmGKIldUGC0bbojSpjZQsgYUTz_JJKUsaluCUWyB7v7v7r37ijaMVd8GbbtODdbFUIlCilwCJHj_D7V3IXjbVHvf9spPFYHqt12V2lV_7ZK9ORyNdW_NUR5iJXB7ACpo1TVeDboNRyck5ZwI9gNky3a8</recordid><startdate>20050701</startdate><enddate>20050701</enddate><creator>YAMAUCHI, Katsumi</creator><creator>YAMAGUCHI, Naoko</creator><creator>SHIRATORI, Keiko</creator><creator>FURUKAWA, Takaji</creator><creator>TAKATSU, Kazuko</creator><creator>NAKANISHI, Toshimi</creator><creator>ISHIDA, Kohji</creator><creator>KOMATSU, Tatsuji</creator><creator>TOKUSHIGE, Katsutoshi</creator><creator>NAGAHARA, Hikaru</creator><creator>HASHIMOTO, Etsuko</creator><general>Wiley</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>7X8</scope></search><sort><creationdate>20050701</creationdate><title>A murine model of acute liver injury induced by human monoclonal autoantibody</title><author>YAMAUCHI, Katsumi ; YAMAGUCHI, Naoko ; SHIRATORI, Keiko ; FURUKAWA, Takaji ; TAKATSU, Kazuko ; NAKANISHI, Toshimi ; ISHIDA, Kohji ; KOMATSU, Tatsuji ; TOKUSHIGE, Katsutoshi ; NAGAHARA, Hikaru ; HASHIMOTO, Etsuko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c313t-3d09d4189bd370f2d61646d774a26dc9f5d1acdbd083f0a51529d37997be80da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Autoantibodies - adverse effects</topic><topic>Autoantibodies - immunology</topic><topic>Biological and medical sciences</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepatitis, Autoimmune - immunology</topic><topic>Hepatocytes - immunology</topic><topic>Hepatocytes - pathology</topic><topic>Humans</topic><topic>Immunoglobulin M - adverse effects</topic><topic>Immunoglobulin M - immunology</topic><topic>Liver Failure, Acute - immunology</topic><topic>Liver. Bile. Biliary tracts</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Models, Animal</topic><topic>Necrosis</topic><topic>Other diseases. Semiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Toxicity: digestive system</topic><topic>Vertebrates: digestive system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>YAMAUCHI, Katsumi</creatorcontrib><creatorcontrib>YAMAGUCHI, Naoko</creatorcontrib><creatorcontrib>SHIRATORI, Keiko</creatorcontrib><creatorcontrib>FURUKAWA, Takaji</creatorcontrib><creatorcontrib>TAKATSU, Kazuko</creatorcontrib><creatorcontrib>NAKANISHI, Toshimi</creatorcontrib><creatorcontrib>ISHIDA, Kohji</creatorcontrib><creatorcontrib>KOMATSU, Tatsuji</creatorcontrib><creatorcontrib>TOKUSHIGE, Katsutoshi</creatorcontrib><creatorcontrib>NAGAHARA, Hikaru</creatorcontrib><creatorcontrib>HASHIMOTO, Etsuko</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>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>YAMAUCHI, Katsumi</au><au>YAMAGUCHI, Naoko</au><au>SHIRATORI, Keiko</au><au>FURUKAWA, Takaji</au><au>TAKATSU, Kazuko</au><au>NAKANISHI, Toshimi</au><au>ISHIDA, Kohji</au><au>KOMATSU, Tatsuji</au><au>TOKUSHIGE, Katsutoshi</au><au>NAGAHARA, Hikaru</au><au>HASHIMOTO, Etsuko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A murine model of acute liver injury induced by human monoclonal autoantibody</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2005-07-01</date><risdate>2005</risdate><volume>42</volume><issue>1</issue><spage>149</spage><epage>155</epage><pages>149-155</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH.</abstract><cop>Hoboken, NJ</cop><pub>Wiley</pub><pmid>15918155</pmid><doi>10.1002/hep.20726</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - immunology Autoantibodies - adverse effects Autoantibodies - immunology Biological and medical sciences Drug toxicity and drugs side effects treatment Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen Hepatitis, Autoimmune - immunology Hepatocytes - immunology Hepatocytes - pathology Humans Immunoglobulin M - adverse effects Immunoglobulin M - immunology Liver Failure, Acute - immunology Liver. Bile. Biliary tracts Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Mice Models, Animal Necrosis Other diseases. Semiology Pharmacology. Drug treatments Toxicity: digestive system Vertebrates: digestive system |
| title | A murine model of acute liver injury induced by human monoclonal autoantibody |
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