Macrophages retain hematopoietic stem cells in the spleen via VCAM-1
Open accessAbstract
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.
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Membrane VCAM1 is expressed on CD169+ macrophages in the spleen and provides a molecular anchor to retain hematopoietic stem cells in the murine spleen.
“In addition, membrane VCAM1 is expressed on CD169+ macrophages in the spleen and provides a molecular anchor to retain hematopoietic stem cells in the murine spleen, although it is unclear whether this is also relevant to arthropathy [61].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [61]
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- Authors
- Dutta, P., Hoyer, F. F., Grigoryeva, L. S., Sager, H. B., Leuschner, F., Courties, G., Borodovsky, A., Novobrantseva, T., Ruda, V. M., Fitzgerald, K., Iwamoto, Y., Wojtkiewicz, G., Sun, Y., Da Silva, N., Libby, P., Anderson, D. G., Swirski, F. K., Weissleder, R., & Nahrendorf, M.
- Affiliations
- Harvard University (US)
- University Hospital Heidelberg (DE)
- Alnylam Pharmaceuticals (United States) (US)
- Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 1
- Brigham and Women's Hospital (US)
- Corresponding author
- Dutta, Partha
- Nahrendorf, Matthias
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2015-03-23
- Volume
- 212
- Issue
- 4
- Pages
- 497-512
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC4387283
- OpenAlex
- W2116562617
- Cited by
- 180
- References
- 53
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 14 · 2023: 10 · 2022: 17 · 2021: 22 · 2020: 15 · 2019: 16 · 2018: 23 · 2017: 12 · 2016: 19 · 2015: 8
- FWCI
- 16.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- HAL (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- U.S. Public Health Service (HHSN 268201000044C)
- National Heart, Lung, and Blood Institute (R01HL117829, HHSN268201000044C, R01HL114477, R00HL121076, K99HL121076)
- National Institute of Neurological Disorders and Stroke (R01NS084863)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD069623)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- hematopoietic stem cells, spleen, macrophages, VCAM-1, splenic red pulp, M-CSF receptor, leukocytosis, myocardial infarction, atherosclerosis, CD169, inflammation, atherosclerotic plaque
- MeSH terms
- Animals, Apolipoproteins E, Gene Expression Regulation, Hematopoiesis, Extramedullary, Hematopoietic Stem Cells, Macrophages, Myocardial Infarction, Spleen, Receptor, Macrophage Colony-Stimulating Factor, Mice, Knockout, Vascular Cell Adhesion Molecule-1, RNA Interference, Myelopoiesis, Atherosclerosis, Mice, Nanoparticles, Plaque, Atherosclerotic, Sialic Acid Binding Ig-like Lectin 1
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