CXCL4-induced plaque macrophages can be specifically identified by co-expression of MMP7+S100A8+ in vitro and in vivo: $hChristian Erbel, Mirjam Tyka, Christian M. Helmes, Mohmmadreza Akhavanpoor, Gregor Rupp, Gabriele Domschke, Fabian Linden, Antonia Wolf, Andreas Doesch, Felix Lasitschka, Hugo A. Katus and Christian A. Gleissner
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 ‘M4’. Here, we sought to identify s...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2015
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| In: |
Innate immunity
Year: 2014, Volume: 21, Issue: 3, Pages: 255-265 |
| ISSN: | 1753-4267 |
| DOI: | 10.1177/1753425914526461 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1177/1753425914526461 Verlag, lizenzpflichtig, Volltext: https://journals.sagepub.com/doi/10.1177/1753425914526461 
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| Summary: | 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 ‘M4’. Here, we sought to identify suitable markers that identify M4 macrophages in vitro and in vivo. 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+MMP7+, CD68+MMP7−, CD68+S100A8+ and CD68+S100A8− macrophages. A small proportion of MMP7+S100A8+ 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. |
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| Item Description: | Im Titel sind die "+"-Zeichen hochgestellt Article first published online: March 24, 2014 Gesehen am 16.07.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1753-4267 |
| DOI: | 10.1177/1753425914526461 |