Macrophages retain hematopoietic stem cells in the spleen via VCAM-1
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 (...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Rockefeller University Press
2015
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| Online Access: | http://hdl.handle.net/1721.1/98402 https://orcid.org/0000-0001-5629-4798 |
| _version_ | 1811091554354331648 |
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| author | 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 Iwamoto, Yoshiko Wojtkiewicz, Gregory Sun, Yuan Da Silva, Nicolas Libby, Peter Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias Anderson, Daniel Griffith |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science 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 Iwamoto, Yoshiko Wojtkiewicz, Gregory Sun, Yuan Da Silva, Nicolas Libby, Peter Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias Anderson, Daniel Griffith |
| author_sort | Dutta, Partha |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:04:12Z |
| format | Article |
| id | mit-1721.1/98402 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:04:12Z |
| publishDate | 2015 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/984022022-09-29T12:25:18Z Macrophages retain hematopoietic stem cells in the spleen via VCAM-1 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 Iwamoto, Yoshiko Wojtkiewicz, Gregory Sun, Yuan Da Silva, Nicolas Libby, Peter Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias Anderson, Daniel Griffith 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 Anderson, Daniel Griffith 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. 2015-09-08T17:38:14Z 2015-09-08T17:38:14Z 2015-03 2014-08 Article http://purl.org/eprint/type/JournalArticle 0022-1007 1540-9538 http://hdl.handle.net/1721.1/98402 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. https://orcid.org/0000-0001-5629-4798 en_US http://dx.doi.org/10.1084/jem.20141642 Journal of Experimental Medicine Creative Commons Attribution http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press Rockefeller University Press |
| spellingShingle | 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 Iwamoto, Yoshiko Wojtkiewicz, Gregory Sun, Yuan Da Silva, Nicolas Libby, Peter Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias Anderson, Daniel Griffith Macrophages retain hematopoietic stem cells in the spleen via VCAM-1 |
| title | Macrophages retain hematopoietic stem cells in the spleen via VCAM-1 |
| title_full | Macrophages retain hematopoietic stem cells in the spleen via VCAM-1 |
| title_fullStr | Macrophages retain hematopoietic stem cells in the spleen via VCAM-1 |
| title_full_unstemmed | Macrophages retain hematopoietic stem cells in the spleen via VCAM-1 |
| title_short | Macrophages retain hematopoietic stem cells in the spleen via VCAM-1 |
| title_sort | macrophages retain hematopoietic stem cells in the spleen via vcam 1 |
| url | http://hdl.handle.net/1721.1/98402 https://orcid.org/0000-0001-5629-4798 |
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