Extramedullary Hematopoiesis Generates Ly-6C(high) Monocytes That Infiltrate Atherosclerotic Lesions

Article

关键词: COLONY-STIMULATING FACTOR;    SPLENIC MARGINAL ZONE;    DENDRITIC CELLS;    DEFICIENT MICE;    B-LYMPHOCYTES;    INFLAMMATION;    MACROPHAGES;    STEM;    SPLEEN;    ORIGIN;   

DOI  :  10.1161/CIRCULATIONAHA.111.061986

来源: SCIE

【 摘 要 】

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. (Circulation. 2012; 125: 364-374.)

【 授权许可】

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