Macrophages retain hematopoietic stem cells in the spleen via VCAM-1
Name
Dutta-2015-Macrophages retain h.pdf
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5.7 MB
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Author(s)
Dutta, Partha
Hoyer, Friedrich Felix
Grigoryeva, Lubov S.
Sager, Hendrik B.
Leuschner, Florian
Courties, Gabriel
Borodovsky, Anna
Novobrantseva, Tatiana I.
Ruda, Vera M.
Fitzgerald, Kevin
Date Issued
March 2015
Journal
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Citation
Dutta, P., F. F. Hoyer, L. S. Grigoryeva, H. B. Sager, F. Leuschner, G. Courties, A. Borodovsky, et al. “Macrophages Retain Hematopoietic Stem Cells in the Spleen via VCAM-1.” Journal of Experimental Medicine 212, no. 4 (March 23, 2015): 497–512.
Version
Final published version
Abstract
Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)[superscript +] macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE[superscript −/−] mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1084/jem.20141642
