| First Author | Robbins CS | Year | 2012 |
| Journal | Circulation | Volume | 125 |
| Issue | 2 | Pages | 364-74 |
| PubMed ID | 22144566 | Mgi Jnum | J:193795 |
| Mgi Id | MGI:5469564 | Doi | 10.1161/CIRCULATIONAHA.111.061986 |
| Citation | Robbins CS, et al. (2012) Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions. Circulation 125(2):364-74 |
| abstractText | BACKGROUND: 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. |
