Monocyte subset dynamics in human atherosclerosis can be profiled with magnetic nano-sensors.
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.
Wildgruber
Moritz
M
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Lee
Hakho
H
Chudnovskiy
Aleksey
A
Yoon
Tae-Jong
TJ
Etzrodt
Martin
M
Pittet
Mikael J
MJ
Nahrendorf
Matthias
M
Croce
Kevin
K
Libby
Peter
P
Weissleder
Ralph
R
Swirski
Filip K
FK
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
D005290:Ferric Compounds; C000499:ferric oxide