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Classical and intermediate monocytes scavenge non-transferrin-bound iron and damaged erythrocytes
David Haschka, … , Guenter Weiss, Piotr Tymoszuk
David Haschka, … , Guenter Weiss, Piotr Tymoszuk
Published April 18, 2019
Citation Information: JCI Insight. 2019;4(8):e98867. https://doi.org/10.1172/jci.insight.98867.
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Research Article Immunology Metabolism

Classical and intermediate monocytes scavenge non-transferrin-bound iron and damaged erythrocytes

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Abstract

Myelomonocytic cells are critically involved in iron turnover as aged RBC recyclers. Human monocytes are divided in 3 subpopulations of classical, intermediate, and nonclassical cells, differing in inflammatory and migratory phenotype. Their functions in iron homeostasis are, however, unclear. Here, we asked whether the functional diversity of monocyte subsets translates into differences in handling physiological and pathological iron species. By microarray data analysis and flow cytometry we identified a set of iron-related genes and proteins upregulated in classical and, in part, intermediate monocytes. These included the iron exporter ferroportin (FPN1), ferritin, transferrin receptor, putative transporters of non-transferrin-bound iron (NTBI), and receptors for damaged erythrocytes. Consequently, classical monocytes displayed superior scavenging capabilities of potentially toxic NTBI, which were augmented by blocking iron export via hepcidin. The same subset and, to a lesser extent, the intermediate population, efficiently cleared damaged erythrocytes in vitro and mediated erythrophagocytosis in vivo in healthy volunteers and patients having received blood transfusions. To summarize, our data underline the physiologically important function of the classical and intermediate subset in clearing NTBI and damaged RBCs. As such, these cells may play a nonnegligible role in iron homeostasis and limit iron toxicity in iron overload conditions.

Authors

David Haschka, Verena Petzer, Florian Kocher, Christoph Tschurtschenthaler, Benedikt Schaefer, Markus Seifert, Sieghart Sopper, Thomas Sonnweber, Clemens Feistritzer, Tara L. Arvedson, Heinz Zoller, Reinhard Stauder, Igor Theurl, Guenter Weiss, Piotr Tymoszuk

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Figure 13

Erythrophagocytosis by blood monocytes in homeostasis and under hematological stress.

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Erythrophagocytosis by blood monocytes in homeostasis and under hematolo...
PBMCs were obtained from healthy individuals (n = 16) and patients who had received blood transfusions within the past 24 hours (n = 15). Intracellular CD235a levels (A) and surface FPN1 expression (B) in each monocyte subpopulation were determined by flow cytometry. Monocyte subpopulations were defined as described in Supplemental Figure 14AB (red: classical; gray: intermediate; blue: nonclassical monocytes). Representative CD235a and FPN1 histograms are shown (tinted histograms: specific antibody staining; open histograms: isotype). Graphs show ΔMFI values. Each point represents 1 measurement, bars denote mean, and error bars represent SEM. Statistical significance for basal CD235a and FPN1 levels in controls and the control-transfused differences were determined with first-order linear models. Separate models were applied to each monocyte subset. Estimate values with 95% CI are shown. Estimate P values were calculated with 2-tailed t test. ANOVA statistics are presented in Supplemental Table 8.

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