Robbins, Clinton S.Chudnovskiy, AlekseyRauch, Philipp J.Figueiredo, Jose-LuizIwamoto, YoshikoGorbatov, RosticEtzrodt, MartinWeber, Georg F.Ueno, TakuyaRooijen, Nico vanMulligan-Kehoe, Mary JoLibby, PeterNahrendorf, MatthiasPittet, Mikael J.Weissleder, RalphSwirski, Filip K.2019-09-212012Robbins, Clinton S., Aleksey Chudnovskiy, Philipp J. Rauch, Jose-Luiz Figueiredo, Yoshiko Iwamoto, Rostic Gorbatov, Martin Etzrodt, et al. 2012. “Extramedullary Hematopoiesis Generates Ly-6C High Monocytes That Infiltrate Atherosclerotic Lesions.” Circulation 125 (2): 364–74. https://doi.org/10.1161/circulationaha.111.061986.0009-73220069-41931524-4539http://nrs.harvard.edu/urn-3:HUL.InstRepos:41384259Background-Atherosclerotic lesions are believed to grow via the recruitment of bone marrow-derived monocytes. Among the known murine monocyte subsets, Ly-6C(high) monocytes are inflammatory, accumulate in lesions preferentially, and differentiate. Here, we hypothesized that the bone marrow outsources the production of Ly-6C(high) monocytes during atherosclerosis. Methods: and Results-Using murine models of atherosclerosis and fate-mapping approaches, we show that hematopoietic stem and progenitor cells progressively relocate from the bone marrow to the splenic red pulp, where they encounter granulocyte macrophage colony-stimulating factor and interleukin-3, clonally expand, and differentiate to Ly-6C(high) monocytes. Monocytes born in such extramedullary niches intravasate, circulate, and accumulate abundantly in atheromata. On lesional infiltration, Ly-6C(high) monocytes secrete inflammatory cytokines, reactive oxygen species, and proteases. Eventually, they ingest lipids and become foam cells. Conclusions: -Our findings indicate that extramedullary sites supplement the hematopoietic function of the bone marrow by producing circulating inflammatory cells that infiltrate atherosclerotic lesions. (Circulation. 2012; 125: 364-374.)en-USJournal Article2019-09-2110.1161/CIRCULATIONAHA.111.061986