Monocyte MRI Relaxation Rates are Regulated by Extracellular Iron and Hepcidin

Praveen S.B Dassanayake, The University of Western Ontario

Abstract

Monocytes are an important immune cell type in chronic inflammatory conditions like atherosclerosis and heart failure. The increase in number of monocytes released to the peripheral blood circulation, the differentiation of monocytes to macrophages, and the presence of different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury may provide markers for monitoring inflammation. In particular, changes in monocyte iron metabolism during an inflammatory response may increase the possibility of tracking these immune cells non-invasively using magnetic resonance imaging (MRI). When secretion of the polypeptide hormone hepcidin is stimulated during inflammation, it binds the iron export protein ferroportin (FPN) on a limited number of cell types, including monocytes and macrophages. This ligand-receptor interaction leads to FPN internalization and downregulation through ubiquitin-mediated degradation. We hypothesized that hepcidin-mediated changes in monocyte iron regulation influence both cellular iron content and magnetic resonance (MR) relaxation rates. In response to varying conditions of extracellular iron supplementation, we observed THP-1 expression of FPN protein and its downregulation following hepcidin treatment. Also, in the presence hepcidin and iron supplementation, we detected a significant increase in the total transverse relaxation rate, R₂*, compared to non-supplemented cells. The positive correlation between total cellular iron content and R₂* improved from moderate to strong in the presence of hepcidin. These in vitro findings suggest that hepcidin-mediated changes detected in monocytes using MRI could be valuable for cell tracking in vivo during an inflammatory response.