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Circulation. 2012 Jan 17;125(2):364-74. doi: 10.1161/CIRCULATIONAHA.111.061986. Epub 2011 Dec 5.

Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions.

Author information

  • 1Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Simches Research Bldg, 185 Cambridge St, Boston, MA 02114, USA. robbins.clinton@mgh.harvard.edu

Abstract

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.

© 2011 American Heart Association, Inc.

PMID:
22144566
[PubMed - indexed for MEDLINE]
PMCID:
PMC3263762
Free PMC Article

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