Monocyte Subset Dynamics in Human Atherosclerosis

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 ml sample size and high throughput capabilities, we then show that application of the model accurately quantifies subset fluctuations that occur in patients with atherosclerosis. Citation: Wildgruber M, Lee H, Chudnovskiy A, Yoon T-J, Etzrodt M, et al. (2009) Monocyte Subset Dynamics in Human Atherosclerosis Can Be Profiled with Magnetic Nano-Sensors. PLoS ONE 4(5): e5663. doi:10.1371/journal.pone.0005663 Editor: Terry Means, Massachusetts General Hospital/Harvard University, United States of America Received April 13, 2009; Accepted April 27, 2009; Published May 22, 2009 Copyright: 2009 Wildgruber et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported in part by NIH grants R01-Eb004626, U01 HL080731, P50 CA86355, R24 CA69246 and P01-A154904 (to R.W.) and the The D.W. Reynolds Clinical Cardiovascular Research Center at Harvard Medical School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: rweissleder@mgh.harvard.edu (RW); fswirski@mgh.harvard.edu (FKS)