Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
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.
View: Text | PDF
Research Article Immunology Metabolism

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

  • Text
  • PDF
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

×

Figure 11

Uptake of damaged erythrocytes by human monocytes in vitro.

Options: View larger image (or click on image) Download as PowerPoint
Uptake of damaged erythrocytes by human monocytes in vitro.
PBMCs were i...
PBMCs were incubated with PKH26-labeled heat-stressed RBCs (A, n = 5 healthy donors) at a ratio of 10 RBCs per PBMC for the indicated time points. PKH26 positivity in monocyte subpopulations was determined by flow cytometry. Monocyte subpopulations were defined as described in Supplemental Figure 2A (red: classical; gray: intermediate; blue: nonclassical monocytes). Representative cytometry plots are shown. Graphs show percentages of PKH26+ cells in each monocyte subset. Each point represents 1 measurement, bars denote mean, and error bars represent SEM. The donor is represented by symbol shape. RBC uptake rate in classical monocytes and differences in uptake rate between classical monocytes and the particular subset were determined with a second-order linear model. All estimates are shown with 95% CI. Estimate P values were calculated with 2-tailed t test. ANOVA statistics are presented in Supplemental Table 7.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts