{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:19:32Z","timestamp":1792448372177,"version":"4.5.0"},"reference-count":44,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2014,3,24]],"date-time":"2014-03-24T00:00:00Z","timestamp":1395619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Innate Immun"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>\n                    Macrophage heterogeneity in human atherosclerotic plaques has been recognized; however, markers for unequivocal identification of some subtypes are lacking. We found that the platelet chemokine CXCL4 induces a unique macrophage phenotype, which we proposed to call \u2018M4\u2019. Here, we sought to identify suitable markers that identify M4 macrophages in\u00a0vitro and in\u00a0vivo. Using a stringent algorithm, we identified a set of potential markers from transcriptomic data derived from polarized macrophages. We specifically focused on matrix metalloproteinase (MMP)7 and S100A8, the co-expression of which has not been described in any macrophage type thus far. We found dose- and time-dependent MMP7 and S100A8 expression in M4 macrophages at the gene and protein levels. CXCL4-induced up-regulation of both MMP7 and S100A8 was curbed in the presence of heparin, which binds to CXCL4 and glycosaminoglycans, most likely representing the macrophage receptor for CXCL4. Immunofluorescence of post-mortem atherosclerotic coronary arteries identified CD68\n                    <jats:sup>+<\/jats:sup>\n                    MMP7\n                    <jats:sup>+<\/jats:sup>\n                    , CD68\n                    <jats:sup>+<\/jats:sup>\n                    MMP7\n                    <jats:sup>\u2212<\/jats:sup>\n                    , CD68\n                    <jats:sup>+<\/jats:sup>\n                    S100A8\n                    <jats:sup>+<\/jats:sup>\n                    and CD68\n                    <jats:sup>+<\/jats:sup>\n                    S100A8\n                    <jats:sup>\u2212<\/jats:sup>\n                    macrophages. A small proportion of MMP7\n                    <jats:sup>+<\/jats:sup>\n                    S100A8\n                    <jats:sup>+<\/jats:sup>\n                    macrophages most likely represent M4 macrophages. In summary, we have identified co-expression of MMP7 and S100A8 to be a marker combination exclusively found in M4 macrophages. This finding may allow further dissection of the role of M4 macrophages in atherosclerosis and other pathologic conditions.\n                  <\/jats:p>","DOI":"10.1177\/1753425914526461","type":"journal-article","created":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T01:23:56Z","timestamp":1395710636000},"page":"255-265","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":101,"title":["CXCL4-induced plaque macrophages can be specifically identified by co-expression of MMP7\n                    <sup>+<\/sup>\n                    S100A8\n                    <sup>+<\/sup>\n                    <i>in\u00a0vitro<\/i>\n                    and\n                    <i>in\u00a0vivo<\/i>"],"prefix":"10.1177","volume":"21","author":[{"given":"Christian","family":"Erbel","sequence":"first","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Tyka","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M","family":"Helmes","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohmmadreza","family":"Akhavanpoor","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Rupp","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Domschke","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Linden","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Doesch","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Lasitschka","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo A","family":"Katus","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A","family":"Gleissner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,3,24]]},"reference":[{"key":"bibr1-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141988"},{"key":"bibr2-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1038\/nri1733"},{"key":"bibr3-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132620"},{"key":"bibr4-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.221127"},{"key":"bibr5-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3258"},{"key":"bibr6-1753425914526461","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7303"},{"key":"bibr7-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00051.2006"},{"key":"bibr8-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.04.005"},{"key":"bibr9-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30992"},{"key":"bibr10-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2008.11.009"},{"key":"bibr11-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.09.015"},{"key":"bibr12-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.06.010"},{"key":"bibr13-1753425914526461","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070513"},{"key":"bibr14-1753425914526461","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080431"},{"key":"bibr15-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.225813"},{"key":"bibr16-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.10.852"},{"key":"bibr17-1753425914526461","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901368"},{"key":"bibr18-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1160\/TH03-02-0069"},{"key":"bibr19-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-06-2475"},{"key":"bibr20-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.4.1158.004k31_1158_1166"},{"key":"bibr21-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-04-0271"},{"key":"bibr22-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.199505"},{"key":"bibr23-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00051.2006"},{"key":"bibr24-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.199505"},{"key":"bibr25-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gng154"},{"key":"bibr26-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg264"},{"key":"bibr27-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V58.3.607.607"},{"key":"bibr28-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1645072"},{"key":"bibr29-1753425914526461","doi-asserted-by":"publisher","DOI":"10.2174\/157016110790886983"},{"key":"bibr30-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1160\/TH11-05-0320"},{"key":"bibr31-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.300173"},{"key":"bibr32-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1038\/nm1102-1235"},{"key":"bibr33-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.1.287"},{"key":"bibr34-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080908"},{"key":"bibr35-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.173898"},{"key":"bibr36-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq042"},{"key":"bibr37-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.10299"},{"key":"bibr38-1753425914526461","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.8.1979"},{"key":"bibr39-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1002\/art.20720"},{"key":"bibr40-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2007.08.018"},{"key":"bibr41-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069395"},{"key":"bibr42-1753425914526461","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.5.2692"},{"key":"bibr43-1753425914526461","first-page":"345","volume-title":"Atherogenesis.","author":"Gleissner CA","year":"2012"},{"key":"bibr44-1753425914526461","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222878110"}],"container-title":["Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425914526461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1753425914526461","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425914526461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:01:57Z","timestamp":1777460517000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1753425914526461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,24]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,4]]}},"alternative-id":["10.1177\/1753425914526461"],"URL":"https:\/\/doi.org\/10.1177\/1753425914526461","relation":{},"ISSN":["1753-4259","1753-4267"],"issn-type":[{"value":"1753-4259","type":"print"},{"value":"1753-4267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,24]]}}}