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Science 31 July 2009:
Vol. 325. no. 5940, pp. 612 - 616
DOI: 10.1126/science.1175202

Reports

Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites

Filip K. Swirski,1,*,{dagger} Matthias Nahrendorf,1,* Martin Etzrodt,1,2 Moritz Wildgruber,1 Virna Cortez-Retamozo,1 Peter Panizzi,1 Jose-Luiz Figueiredo,1 Rainer H. Kohler,1 Aleksey Chudnovskiy,1 Peter Waterman,1 Elena Aikawa,1 Thorsten R. Mempel,1,3 Peter Libby,4,5 Ralph Weissleder,1,6,{dagger} Mikael J. Pittet1,{dagger}

A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.

1 Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
2 Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
3 Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
4 Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.
5 Center for Excellence in Vascular Biology, Brigham and Women’s Hospital, Boston, MA 02115, USA.
6 Department of Systems Biology, Harvard Medical School, Boston, MA 02115.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: fswirski{at}mgh.harvard.edu (F.K.S.); rweissleder{at}mgh.harvard.edu (R.W.); mpittet{at}mgh.harvard.edu (M.J.P.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)