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Progressive replacement of embryo-derived cardiac macrophages with age

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Item Type:Article
Title:Progressive replacement of embryo-derived cardiac macrophages with age
Creators Name:Molawi, K. and Wolf, Y. and Kandalla, P.K. and Favret, J. and Hagemeyer, N. and Frenzel, K. and Pinto, A.R. and Klapproth, K. and Henri, S. and Malissen, B. and Rodewald, H.R. and Rosenthal, N.A. and Bajenoff, M. and Prinz, M. and Jung, S. and Sieweke, M.H.
Abstract:Cardiac macrophages (cMPhi) are critical for early postnatal heart regeneration and fibrotic repair in the adult heart, but their origins and cellular dynamics during postnatal development have not been well characterized. Tissue macrophages can be derived from embryonic progenitors or from monocytes during inflammation. We report that within the first weeks after birth, the embryo-derived population of resident CX3CR1+ cMPhi diversifies into MHCII+ and MHCII- cells. Genetic fate mapping demonstrated that cMPhi derived from CX3CR1+ embryonic progenitors persisted into adulthood but the initially high contribution to resident cMPhi declined after birth. Consistent with this, the early significant proliferation rate of resident cMPhi decreased with age upon diversification into subpopulations. Bone marrow (BM) reconstitution experiments showed monocyte-dependent quantitative replacement of all cMPhi populations. Furthermore, parabiotic mice and BM chimeras of nonirradiated recipient mice revealed a slow but significant donor contribution to cMPhi. Together, our observations indicate that in the heart, embryo-derived cMPhi show declining self-renewal with age and are progressively substituted by monocyte-derived macrophages, even in the absence of inflammation.
Keywords:Age Factors, Cell Differentiation, Cell Proliferation, Immunophenotyping, Macrophages, Monocytes, Myocardium, Newborn Animals, Phenotype, Surface Antigens, Transgenic Mice, Animals, Mice
Source:Journal of Experimental Medicine
ISSN:0022-1007
Publisher:Rockefeller University Press (U.S.A.)
Volume:211
Number:11
Page Range:2151-2158
Date:20 October 2014
Official Publication:https://doi.org/10.1084/jem.20140639
PubMed:View item in PubMed

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