2015/03/23 by Partha Dutta, Friedrich Felix Hoyer, Lubov Grigoryeva +16 · 2 citations
Immunology and Microbiology · Neuroscience · #Immune cells in cancer #Neuroinflammation and Neurodegeneration Mechanisms #Neutrophil, Myeloperoxidase and Oxidative Mechanisms
paper · pdf · doi:10.1084/jem.20141642
openalex publication_date 2015/03/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04
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.