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This controversy may stem from the heterogeneity and\/or plasticity of macrophages and the difficulty in distinguishing and differentially studying subpopulations of macrophages in the liver. In the present study, using flow cytometric analysis and fluorescence-labeled antibodies against specific cell surface macrophage markers, we were able to, for the first time, identify an APAP-induced macrophage (IM) population distinct from resident Kupffer cells. The data demonstrated that the IMs were derived from circulating monocytes that infiltrated the liver following APAP-induced liver injury. The IMs exhibited a phenotype consistent with that of alternatively activated macrophages and demonstrated the ability to phagocytize apoptotic cells and induce apoptosis of neutrophils. Furthermore, in the absence of the IMs, the resolution of hepatic damage following APAP-induced hepatotoxicity was delayed in CCR2\u2212\/\u2212 mice compared with wild-type mice. These findings likely contribute to the role of the IMs in the processes of tissue repair, including counteracting inflammation and promoting angiogenesis. The present study also demonstrated the ability of separating populations of macrophages and delineating distinct functions of each group in future studies of inflammatory disease in the liver and other tissues.<\/jats:p>","DOI":"10.1189\/jlb.0308173","type":"journal-article","created":{"date-parts":[[2008,8,20]],"date-time":"2008-08-20T03:52:10Z","timestamp":1219204330000},"page":"1410-1421","source":"Crossref","is-referenced-by-count":364,"title":["Identification and characterization of infiltrating macrophages in acetaminophen-induced liver injury"],"prefix":"10.1093","volume":"84","author":[{"given":"Michael P","family":"Holt","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Colorado Denver , Denver, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LinLing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Colorado Denver , Denver, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Colorado Denver , Denver, Colorado , USA"},{"name":"Department of Integrated Immunology, University of Colorado Denver , Denver, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,8,19]]},"reference":[{"key":"2023032712364711400_","first-page":"CR292","article-title":"Drug-induced liver damage\u2014a three-year study of patients from one gastroenterological department","volume":"8","author":"Hartleb","year":"2002","journal-title":"Med. 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