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Updated: Mar 21, 2026
09:15
Induction of Eryptosis in Red Blood Cells Using a Calcium Ionophore
Published on: January 21, 2020
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Anidulafungin-Induced Suicidal Erythrocyte Death
Summary
Anidulafungin, an antifungal drug, triggers eryptosis, a form of red blood cell death. This process involves cell shrinkage and membrane changes, partly due to calcium influx and p38 kinase activation.
Area of Science:
- Hematology
- Pharmacology
- Cell Biology
Background:
- Anidulafungin is a novel antifungal medication for candidiasis and aspergillosis.
- Amphotericin B, a traditional antifungal, induces eryptosis, characterized by erythrocyte shrinkage and phosphatidylserine exposure.
- Eryptosis is triggered by increased intracellular calcium, oxidative stress, ceramide, and activated kinases (PKC, CK1α, p38), and inhibited by nitric oxide (NO).
Purpose of the Study:
- To investigate whether the antifungal drug Anidulafungin induces eryptosis in human erythrocytes.
- To elucidate the mechanisms involved in Anidulafungin-induced eryptosis.
Main Methods:
- Flow cytometry was used to assess phosphatidylserine externalization (annexin-V binding), cell volume (forward scatter), intracellular calcium ([Ca2+]i), and reactive oxygen species (ROS).
- Ceramide abundance and hemoglobin concentration (for hemolysis) were also measured.
- Specific inhibitors for p38 kinase, PKC, casein kinase 1α, caspases, and antioxidants were employed to explore signaling pathways.
Main Results:
- Anidulafungin exposure (1.5-6 µg/ml) for 48 hours significantly increased hemolysis and annexin-V binding, while decreasing cell volume.
- Anidulafungin elevated intracellular calcium levels, an effect partially dependent on extracellular calcium.
- The eryptosis induction by Anidulafungin was significantly inhibited by a p38 kinase inhibitor and a nitric oxide donor, but not by antioxidants or inhibitors of PKC, CK1α, or caspases.
Conclusions:
- Anidulafungin induces hemolysis and eryptosis in human erythrocytes.
- The observed eryptosis is characterized by cell shrinkage and phospholipid scrambling.
- This effect is partly mediated by calcium influx and the activation of p38 kinase.
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