DescriptionThe origins of tissue macrophages are uncertain, with evidence for both circulatory renewal and local production. Given the intricate relationship between haematopoiesis and the vasculature during embryogenesis, we investigated whether postnatal blood vessels may also harbor hematopoietic stem (HSC) and progenitor cells (HPC). Arterial disaggregates from adult mice can generating the full spectrum of haematopoietic colony forming units in vitro, displaying spatial and temporal heterogeneity. While multipotent HPC and HSC are rare within the vessel wall, adult arteries have marked predilection and enrichment for macrophage colony forming units (CFU-M), compared to traditional haematopoietic and non-haematopoietic tissues. These macrophage progenitor cells are contained within the vascular adventitia, where they co-express Sca-1 and CD45. Adventitial Sca-1+CD45+ progenitors are the predominant source of proliferating cells in aorta and are phenotypically and genotypically distinct from cells lacking Sca-1 or CD45, with upregulation of macrophage markers, chemokine receptors and transcription factors implicated in haematopoiesis and atherosclerosis. As revealed by tracking studies, adventitial macrophage progenitors are of local origin rather than arising from BM or spleen, unlike multipotent HPC which survey the vessel wall via peripheral circulation. Although macrophage-colony stimulating factor is not required for the presence of vascular CFU-M, it does mediate differentiation of progenitor cells to mature macrophage progeny and may partly account for an increase of Sca-1+CD45+ cells and CFU-M in aortas of pro-atherogenic and atherosclerotic mice. The discovery of an enriched source of macrophage progenitor cells in postnatal vascular adventitia has important implications for our understanding of the local production and regulation of tissue macrophages in health and disease.
|Event title||The Australian Health and Medical Research Congress, Adelaide|