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

• DOI: 10.1084/jem.20141642
• Publication Date: 2015-03-24T02:23:15Z
• Authors: Partha Dutta; Friedrich Felix H...; Lubov S. Grigoryeva; Hendrik B. Sager; Florian Leuschner; Gabriel Courties; Anna Borodovsky; Tatiana Novobrant...; 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
• Keywords: Myelopoiesis; Red pulp; Extramedullary hematopoiesis; Leukocytosis; White pulp

Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular adhesion molecule 1 (VCAM-1)(+) macrophages are essential extramedullary because these use VCAM-1 retain HSCs spleen. Nanoparticle-enabled vivo RNAi silencing receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic maturation, reduced expression compromised HSC retention. Both, depleting CD169 iDTR mice or released from When silenced either M-CSFR myocardial infarction ApoE(-/-) atherosclerosis, nanoparticle-enabled mitigated blood leukocytosis, limited inflammation ischemic heart, myeloid numbers atherosclerotic plaques.