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The Human Heart Contains Distinct Macrophage Subsets with Divergent Origins and Functions
Paradigm shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2- and CCR2+ subset...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082687/ https://www.ncbi.nlm.nih.gov/pubmed/29892064 http://dx.doi.org/10.1038/s41591-018-0059-x |
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author | Bajpai, Geetika Schneider, Caralin Wong, Nicole Bredemeyer, Andrea Hulsmans, Maarten Nahrendorf, Matthias Epelman, Slava Kreisel, Daniel Liu, Yongjoan Itoh, Akinobu Shankar, Thirupura S. Selzman, Craig H. Drakos, Stavros G. Lavine, Kory J. |
author_facet | Bajpai, Geetika Schneider, Caralin Wong, Nicole Bredemeyer, Andrea Hulsmans, Maarten Nahrendorf, Matthias Epelman, Slava Kreisel, Daniel Liu, Yongjoan Itoh, Akinobu Shankar, Thirupura S. Selzman, Craig H. Drakos, Stavros G. Lavine, Kory J. |
author_sort | Bajpai, Geetika |
collection | PubMed |
description | Paradigm shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2- and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here we demonstrate that the human myocardium also contains distinct subsets of CCR2- and CCR2+ macrophages. Analysis of sex mismatched heart transplant recipients revealed that CCR2- macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2- and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2- and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with LV remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart. |
format | Online Article Text |
id | pubmed-6082687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-60826872018-12-11 The Human Heart Contains Distinct Macrophage Subsets with Divergent Origins and Functions Bajpai, Geetika Schneider, Caralin Wong, Nicole Bredemeyer, Andrea Hulsmans, Maarten Nahrendorf, Matthias Epelman, Slava Kreisel, Daniel Liu, Yongjoan Itoh, Akinobu Shankar, Thirupura S. Selzman, Craig H. Drakos, Stavros G. Lavine, Kory J. Nat Med Article Paradigm shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2- and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here we demonstrate that the human myocardium also contains distinct subsets of CCR2- and CCR2+ macrophages. Analysis of sex mismatched heart transplant recipients revealed that CCR2- macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2- and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2- and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with LV remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart. 2018-06-11 2018-08 /pmc/articles/PMC6082687/ /pubmed/29892064 http://dx.doi.org/10.1038/s41591-018-0059-x Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Bajpai, Geetika Schneider, Caralin Wong, Nicole Bredemeyer, Andrea Hulsmans, Maarten Nahrendorf, Matthias Epelman, Slava Kreisel, Daniel Liu, Yongjoan Itoh, Akinobu Shankar, Thirupura S. Selzman, Craig H. Drakos, Stavros G. Lavine, Kory J. The Human Heart Contains Distinct Macrophage Subsets with Divergent Origins and Functions |
title | The Human Heart Contains Distinct Macrophage Subsets with Divergent
Origins and Functions |
title_full | The Human Heart Contains Distinct Macrophage Subsets with Divergent
Origins and Functions |
title_fullStr | The Human Heart Contains Distinct Macrophage Subsets with Divergent
Origins and Functions |
title_full_unstemmed | The Human Heart Contains Distinct Macrophage Subsets with Divergent
Origins and Functions |
title_short | The Human Heart Contains Distinct Macrophage Subsets with Divergent
Origins and Functions |
title_sort | human heart contains distinct macrophage subsets with divergent
origins and functions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082687/ https://www.ncbi.nlm.nih.gov/pubmed/29892064 http://dx.doi.org/10.1038/s41591-018-0059-x |
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