Macrophages retain hematopoietic stem cells in the spleen via VCAM-1

Partha Dutta; Friedrich Felix Hoyer; Lubov S. Grigoryeva; Hendrik B. Sager; Florian Leuschner; Gabriel Courties; Anna Borodovsky; Tatiana Novobrantseva; Vera M. Ruda; Kevin Fitzgerald; Yoshiko Iwamoto; Gregory Wojtkiewicz; Yuan Sun; Nicolas Da Silva; Peter Libby; Daniel G. Anderson; Filip K. Swirski; Ralph Weissleder; Matthias Nahrendorf

doi:10.1084/jem.20141642

Macrophages retain hematopoietic stem cells in the spleen via VCAM-1

Partha Dutta, Friedrich Felix Hoyer, Lubov S. Grigoryeva, Hendrik B. Sager, Florian Leuschner, Gabriel Courties, Anna Borodovsky, Tatiana Novobrantseva, Vera M. Ruda, Kevin Fitzgerald, Yoshiko Iwamoto, Gregory Wojtkiewicz, Yuan Sun, Nicolas Da Silva, Peter Libby, Daniel G. Anderson, Filip K. Swirski, Ralph Weissleder, Matthias Nahrendorf

Research output: Contribution to journal › Article › peer-review

130 Scopus citations

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.

Original language	English
Pages (from-to)	497-512
Number of pages	16
Journal	Journal of Experimental Medicine
Volume	212
Issue number	4
DOIs	https://doi.org/10.1084/jem.20141642
State	Published - 6 Apr 2015
Externally published	Yes

Access to Document

10.1084/jem.20141642

Cite this

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. (2015). Macrophages retain hematopoietic stem cells in the spleen via VCAM-1. Journal of Experimental Medicine, 212(4), 497-512. https://doi.org/10.1084/jem.20141642

@article{d2088f8b074c4d8e90fc3b12ee1ce304,

title = "Macrophages retain hematopoietic stem cells in the spleen via VCAM-1",

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.",

author = "Partha Dutta and Hoyer, {Friedrich Felix} and Grigoryeva, {Lubov S.} and Sager, {Hendrik B.} and Florian Leuschner and Gabriel Courties and Anna Borodovsky and Tatiana Novobrantseva and Ruda, {Vera M.} and Kevin Fitzgerald and Yoshiko Iwamoto and Gregory Wojtkiewicz and Yuan Sun and {Da Silva}, Nicolas and Peter Libby and Anderson, {Daniel G.} and Swirski, {Filip K.} and Ralph Weissleder and Matthias Nahrendorf",

note = "Publisher Copyright: {\textcopyright} 2015 Mantovani and Allavena.",

year = "2015",

month = apr,

day = "6",

doi = "10.1084/jem.20141642",

language = "English",

volume = "212",

pages = "497--512",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "4",

}

Dutta, P, Hoyer, FF, Grigoryeva, LS, Sager, HB, Leuschner, F, Courties, G, Borodovsky, A, Novobrantseva, T, Ruda, VM, Fitzgerald, K, Iwamoto, Y, Wojtkiewicz, G, Sun, Y, Da Silva, N, Libby, P, Anderson, DG, Swirski, FK, Weissleder, R & Nahrendorf, M 2015, 'Macrophages retain hematopoietic stem cells in the spleen via VCAM-1', Journal of Experimental Medicine, vol. 212, no. 4, pp. 497-512. https://doi.org/10.1084/jem.20141642

TY - JOUR

T1 - Macrophages retain hematopoietic stem cells in the spleen via VCAM-1

AU - Dutta, Partha

AU - Hoyer, Friedrich Felix

AU - Grigoryeva, Lubov S.

AU - Sager, Hendrik B.

AU - Leuschner, Florian

AU - Courties, Gabriel

AU - Borodovsky, Anna

AU - Novobrantseva, Tatiana

AU - Ruda, Vera M.

AU - Fitzgerald, Kevin

AU - Iwamoto, Yoshiko

AU - Wojtkiewicz, Gregory

AU - Sun, Yuan

AU - Da Silva, Nicolas

AU - Libby, Peter

AU - Anderson, Daniel G.

AU - Swirski, Filip K.

AU - Weissleder, Ralph

AU - Nahrendorf, Matthias

PY - 2015/4/6

Y1 - 2015/4/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84928254121&partnerID=8YFLogxK

U2 - 10.1084/jem.20141642

DO - 10.1084/jem.20141642

M3 - Article

C2 - 25800955

AN - SCOPUS:84928254121

SN - 0022-1007

VL - 212

SP - 497

EP - 512

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 4

ER -

Macrophages retain hematopoietic stem cells in the spleen via VCAM-1

Abstract

Access to Document

Fingerprint

Cite this