Identification of splenic reservoir monocytes and their deployment to inflammatory sites.
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.
Swirski
Filip K
FK
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. fswirski@mgh.harvard.edu
Nahrendorf
Matthias
M
Etzrodt
Martin
M
Wildgruber
Moritz
M
Cortez-Retamozo
Virna
V
Panizzi
Peter
P
Figueiredo
Jose-Luiz
JL
Kohler
Rainer H
RH
Chudnovskiy
Aleksey
A
Waterman
Peter
P
Aikawa
Elena
E
Mempel
Thorsten R
TR
Libby
Peter
P
Weissleder
Ralph
R
Pittet
Mikael J
MJ
D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement; D048429:Cell Size; D005260:Female; D007249:Inflammation / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D009206:Myocardium / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013156:Splenectomy
D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; D011945:Receptors, Angiotensin; D000804:Angiotensin II