The Origin and Maintenance of Resident Aortic Macrophages

Abstract

Macrophages maintain tissues homeostasis, while also contributing to numerous pathological processes, making them attractive targets for therapeutic intervention. Therapeutic design however, requires detailed understanding of macrophage origins, the mechanisms that maintain them, and their functional attributes in tissue- and disease-specific contexts. The origin and maintenance of vascular macrophages in the steady state and inflammation has yet to be elucidated. In the following thesis we establish that the murine aorta contains macrophages derived from embryonic and definitive hematopoietic precursors. We demonstrate that aortic macrophages are maintained locally and are able to replenish following inflammation via proliferation. Microarray analysis revealed two important traits: aortic macrophages are distinct from other tissue resident macrophages and following inflammation aortic macrophages rapidly return to homeostasis. In addition, we identify the CX3CR1-CX3CL1 axis as important for aortic macrophage survival. Taken together, this thesis provides a basis upon which future studies of aortic macrophages may be undertaken.M.Sc.2017-11-24 00:00:0

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