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https://hdl.handle.net/2440/93123
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Type: | Journal article |
Title: | Characterization of a resident population of adventitial macrophage progenitor cells in postnatal vasculature |
Author: | Psaltis, P. Puranik, A. Spoon, D. Chue, C. Hoffman, S. Witt, T. Delacroix, S. Kleppe, L. Mueske, C. Pan, S. Gulati, R. Simari, R. |
Citation: | Circulation Research, 2014; 115(3):364-375 |
Publisher: | Lippincott Williams and Wilkins |
Issue Date: | 2014 |
ISSN: | 0009-7330 1524-4571 |
Statement of Responsibility: | Peter J. Psaltis, Amrutesh S. Puranik, Daniel B. Spoon, Colin D. Chue, Scott J. Hoffman, Tyra A. Witt, Sinny Delacroix, Laurel S. Kleppe, Cheryl S. Mueske, Shuchong Pan, Rajiv Gulati, Robert D. Simari |
Abstract: | RATIONALE: Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal. OBJECTIVE: We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate. METHODS AND RESULTS: Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units. Aorta showed a unique predilection for generating macrophage colony-forming units. Aortic macrophage colony-forming unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially located, where they were the predominant source of proliferating cells in the aortic wall. Aortic Sca-1(+)CD45(+) cells were transcriptionally and phenotypically distinct from neighboring cells lacking stem cell antigen-1 or CD45 and contained a proliferative (Ki67(+)) Lin(-)c-Kit(+)CD135(-)CD115(+)CX3CR1(+)Ly6C(+)CD11b(-) subpopulation, consistent with the immunophenotypic profile of macrophage progenitors. Adoptive transfer studies revealed that Sca-1(+)CD45(+) adventitial macrophage progenitor cells were not replenished via the circulation from bone marrow or spleen, nor was their prevalence diminished by depletion of monocytes or macrophages by liposomal clodronate treatment or genetic deficiency of macrophage colony-stimulating factor. Rather adventitial macrophage progenitor cells were upregulated in hyperlipidemic ApoE(-/-) and LDL-R(-/-) mice, with adventitial transfer experiments demonstrating their durable contribution to macrophage progeny particularly in the adventitia, and to a lesser extent the atheroma, of atherosclerotic carotid arteries. CONCLUSIONS: The discovery and characterization of resident vascular adventitial macrophage progenitor cells provides new insight into adventitial biology and its participation in atherosclerosis and provokes consideration of the broader existence of local macrophage progenitors in other tissues. |
Keywords: | Animals Mice, Inbred C57BL Mice, Knockout Mice Spleen Aorta Macrophages Cell Line Apolipoproteins E Membrane Proteins Receptors, LDL Adoptive Transfer Immunophenotyping Hyperlipidemias Atherosclerosis Antigens, Ly Antigens, CD45 Stem Cells Female Adventitia Male |
Rights: | © 2014 American Heart Association, Inc. |
DOI: | 10.1161/CIRCRESAHA.115.303299 |
Published version: | http://dx.doi.org/10.1161/circresaha.115.303299 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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