Non-Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Progressive replacement of embryo-derived cardiac macrophages with age.

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.