{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T09:49:14Z","timestamp":1770544154090,"version":"3.49.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T00:00:00Z","timestamp":1355356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["APP1003108"],"award-info":[{"award-number":["APP1003108"]}]},{"name":"Queensland Government's Smart State Health and Medical Research Fund"},{"name":"Princess Alexandra Hospital Research and Development Foundation"},{"name":"Sasakawa Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Liver macrophages are a heterogeneous cell population that produces factors involved in fibrogenesis and matrix turnover, including matrix metalloproteinase (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>) \u20109. During liver injury, their close proximity to hepatic progenitor cells and the ductular reaction may enable them to regulate liver repair and fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To enumerate and characterise liver macrophages in patients with chronic hepatitis C, to determine whether a distinct population of macrophages is associated with the ductular reaction and portal fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunostaining for macrophage markers (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>68, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>163, <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2), the ductular reaction (keratin\u20107) and <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109 was performed in liver biopsy sections from patients with chronic hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) (<jats:italic>n<\/jats:italic>\u00a0=\u00a085).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Portal tracts were more densely populated with macrophages (10.5\u00a0\u00b1\u00a00.36 macrophages\/HPF) than lobules (7.2\u00a0\u00b1\u00a00.16 macrophages\/HPF, <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001) and macrophages were found in close proximity to the ductular reaction. \u226530% of portal and periductal macrophages expressed MMP\u20109 and these were significantly associated with increasing stage of fibrosis (<jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>\u00a0=\u00a00.58, 0.68, respectively, both <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001). In contrast, MMP\u20109<jats:sup>+<\/jats:sup> macrophages were largely absent in lobular regions and non\u2010diseased liver. Hepatic MMP\u20109 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels and gelatinolytic activity were significantly associated with stage of fibrosis (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u00a0=\u00a00.47, <jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u00a0=\u00a00.89, respectively, both <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001). Furthermore, a second distinct CCR2<jats:sup>+<\/jats:sup> macrophage population was localised to the centrilobular regions and was predominantly absent from portal and periductal areas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings demonstrate significant regional differences in macrophage phenotypes, suggesting that there are at least two populations of liver macrophages. We propose that these populations have distinct contributions to the pathogenesis of chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010related liver disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12050","type":"journal-article","created":{"date-parts":[[2012,11,12]],"date-time":"2012-11-12T12:00:45Z","timestamp":1352721645000},"page":"569-579","source":"Crossref","is-referenced-by-count":40,"title":["Portal, but not lobular, macrophages express matrix metalloproteinase\u20109: association with the ductular reaction and fibrosis in chronic hepatitis C"],"prefix":"10.1111","volume":"33","author":[{"given":"Victoria L.","family":"Gadd","sequence":"first","affiliation":[{"name":"Centre for Liver Disease Research School of Medicine The University of Queensland Princess Alexandra Hospital Brisbane Qld Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Melino","sequence":"additional","affiliation":[{"name":"Centre for Liver Disease Research School of Medicine The University of Queensland Princess Alexandra Hospital Brisbane Qld Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Roy","sequence":"additional","affiliation":[{"name":"Diamantina Institute The University of Queensland Brisbane Qld Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leigh","family":"Horsfall","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Princess Alexandra Hospital Brisbane Qld Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"O'Rourke","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research Brisbane Qld Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Millicent R.","family":"Williams","sequence":"additional","affiliation":[{"name":"Centre for Liver Disease Research School of Medicine The University of Queensland Princess Alexandra Hospital Brisbane Qld Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharine M.","family":"Irvine","sequence":"additional","affiliation":[{"name":"Centre for Liver Disease Research School of Medicine The University of Queensland Princess Alexandra Hospital Brisbane Qld Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Sweet","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre The University of Queensland Brisbane Qld Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie R.","family":"Jonsson","sequence":"additional","affiliation":[{"name":"Centre for 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