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Macrophages retain hematopoietic stem cells in the spleen via VCAM-1.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2015 Apr 06; Vol. 212 (4), pp. 497-512. Date of Electronic Publication: 2015 Mar 23. - Publication Year :
- 2015
-
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)(+) 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(-/-) 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.<br /> (© 2015 Dutta et al.)
- Subjects :
- Animals
Apolipoproteins E genetics
Apolipoproteins E immunology
Atherosclerosis genetics
Atherosclerosis immunology
Atherosclerosis pathology
Gene Expression Regulation genetics
Gene Expression Regulation immunology
Hematopoiesis, Extramedullary genetics
Hematopoietic Stem Cells pathology
Macrophages pathology
Mice
Mice, Knockout
Myelopoiesis genetics
Myocardial Infarction genetics
Myocardial Infarction immunology
Myocardial Infarction pathology
Nanoparticles
Plaque, Atherosclerotic genetics
Plaque, Atherosclerotic immunology
Plaque, Atherosclerotic pathology
RNA Interference
Receptor, Macrophage Colony-Stimulating Factor genetics
Receptor, Macrophage Colony-Stimulating Factor immunology
Sialic Acid Binding Ig-like Lectin 1 genetics
Sialic Acid Binding Ig-like Lectin 1 immunology
Spleen pathology
Vascular Cell Adhesion Molecule-1 genetics
Hematopoiesis, Extramedullary immunology
Hematopoietic Stem Cells immunology
Macrophages immunology
Myelopoiesis immunology
Spleen immunology
Vascular Cell Adhesion Molecule-1 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 212
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25800955
- Full Text :
- https://doi.org/10.1084/jem.20141642