Non-heme iron overload impairs monocyte to macrophage differentiation via mitochondrial oxidative stress

• DOI: 10.3389/fimmu.2022.998059
• Publication Date: 2022-10-21T07:48:24Z
• Authors: Yue Cui; Saray Gutierrez; Sheller Ariai; Lisa Öberg; Kristofer Thörn; Ulf Gehrmann; Suzanne M. Cloonan; Thomas Naessens; Henric Olsson
• Keywords: HMOX1; Ferroportin; Mitochondrial ROS

Iron is a key element for systemic oxygen delivery and cellular energy metabolism. Thus regulation of local iron metabolism maintaining homeostasis. Significant changes in levels due to malnutrition or hemorrhage, have been associated with several diseases such as hemochromatosis, liver cirrhosis COPD. Macrophages are cells regulating tissues they sequester excess iron. How overload affects macrophage differentiation function remains subject debate. Here we used an vitro model monocyte-to-macrophage study the effect on function. We found that providing soluble ferric ammonium citrate (FAC) rather than heme-iron complexes derived from stressed red blood (sRBC) interferes phagocytosis. Impaired coincided increased expression oxidative stress-related genes. Addition FAC also led mitochondrial reactive species (ROS) interfered ATP generation. The effects were reproduced by ROS-inducer rotenone while treatment ROS-scavenger N-Acetylcysteine partially reversed FAC-induced effects. Finally, iron-induced stress upregulation M-CSFR MAFB, two crucial determinants In summary, our findings suggest high non-heme interfere inducing stress. These might be important consider context like chronic obstructive pulmonary disease (COPD) where both defective suggested play role pathogenesis.