title: Monocyte subset dynamics in human atherosclerosis can be profiled with magnetic nano-sensors.
abstract: Monocytes are circulating macrophage and dendritic cell precursors that populate healthy and diseased tissue. In humans, monocytes consist of at least two subsets whose proportions in the blood fluctuate in response to coronary artery disease, sepsis, and viral infection. Animal studies have shown that specific shifts in the monocyte subset repertoire either exacerbate or attenuate disease, suggesting a role for monocyte subsets as biomarkers and therapeutic targets. Assays are therefore needed that can selectively and rapidly enumerate monocytes and their subsets. This study shows that two major human monocyte subsets express similar levels of the receptor for macrophage colony stimulating factor (MCSFR) but differ in their phagocytic capacity. We exploit these properties and custom-engineer magnetic nanoparticles for ex vivo sensing of monocytes and their subsets. We present a two-dimensional enumerative mathematical model that simultaneously reports number and proportion of monocyte subsets in a small volume of human blood. Using a recently described diagnostic magnetic resonance (DMR) chip with 1 microl sample size and high throughput capabilities, we then show that application of the model accurately quantifies subset fluctuations that occur in patients with atherosclerosis.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Moritz
authors.initials: M
authors.lastname: Wildgruber
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
authors.forename: Aleksey
authors.initials: A
authors.lastname: Chudnovskiy
authors.forename: Tae-Jong
authors.initials: TJ
authors.lastname: Yoon
authors.forename: Martin
authors.initials: M
authors.lastname: Etzrodt
authors.forename: Mikael J
authors.initials: MJ
authors.lastname: Pittet
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Kevin
authors.initials: K
authors.lastname: Croce
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
mesh_terms: D050197:Atherosclerosis / Q000276:immunology*; D015374:Biosensing Techniques / Q000295:instrumentation*; D005290:Ferric Compounds / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics / Q000295:instrumentation*; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology*; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000295:instrumentation*; D010641:Phenotype; D013194:Staining and Labeling
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide