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Updated: Feb 11, 2026
Induction of Eryptosis in Red Blood Cells Using a Calcium Ionophore
Published on: January 21, 2020
Eryptosis in Haemochromatosis: Implications for rheology
Jeanette N du Plooy1, Janette Bester1, Etheresia Pretorius2
1Department of Physiology, University of Pretoria, South Africa.
Background:
Haemochromatosis is an iron-storage disease with different genetic mutations, characterized by an increased intestinal absorption of iron, resulting in a deposition of excessive amounts of iron in parenchymal cells. When the iron is released in the blood, it is left in an unliganded form, where it can participate in Haber-Weiss and Fenton reactions, creating hydroxyl radicals. Erythrocytes (RBCs) are particularly vulnerable to hydroxyl radical damage, which can result in eryptosis (programmed cell death similar to apoptosis).
Study Design And Methods:
Here, we used flow cytometry to study the presence of eryptosis in the main genotypic variations of HFE (heterozygous and homozygous C282Y; H63D; C282Y/H63D). We also viewed RBCs from the different mutations using super-resolution Airyscan confocal microscopy.
Results:
Flow cytometry showed significant changes in membrane biochemistry, indicated by the presence of phosphatidylserine (PS) proteins on the outer leaflet of the membrane, as well as increased intracellular calpain. This was found in all of the studied mutations. Airyscan fluorescence revealed PS flip and also microparticles from RBCs. Such microparticles are known to be pro-inflammatory.
Conclusion:
We conclude that RBC pathology is present in all the studied HFE mutations, even in low penetrance mutations, and this might affect rheology in these individuals.
