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Red Blood Cells Store and Release Interleukin-33
Jianxin Wei1, Jing Zhao, Valerie Schrott
1From *Department of Medicine, †Acute Lung Injury Center of Excellence, ‡Vascular Medicine Institute, §Department of Pathology, and ∥Department of Cell Biology, University of Pittsburgh, PA.
Summary
Red blood cells (RBCs) are a major source of Interleukin-33 (IL-33), a cytokine linked to inflammation. Upon hemolysis, RBCs release IL-33, potentially contributing to inflammatory disease pathogenesis.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Interleukin-33 (IL-33) is a cytokine implicated in inflammatory diseases.
- IL-33 is released from damaged cells and elevated in various conditions like asthma and dermatitis.
- The cellular sources and release mechanisms of IL-33 are not fully understood.
Purpose of the Study:
- To investigate red blood cells (RBCs) as a source of Interleukin-33 (IL-33).
- To determine the correlation between hemolysis and plasma IL-33 levels.
- To explore the functional role of IL-33 released from RBCs.
Main Methods:
- Quantification of IL-33 in lysed RBC supernatants.
- Measurement of plasma IL-33 levels in patients experiencing hemolysis.
- Detection of IL-33 expression in erythroid progenitor cells.
- Assessing IL-8 induction by hemoglobin-depleted RBC lysates in epithelial cells.
Main Results:
- Significantly increased IL-33 levels were observed in supernatants from lysed RBCs.
- Plasma IL-33 levels positively correlated with the degree of hemolysis in patients.
- IL-33 protein and mRNA were detected in late-stage differentiating erythroid progenitor cells.
- Hemoglobin-depleted RBC lysates induced IL-8 expression, an effect modulated by IL-33 receptors.
Conclusions:
- Circulating RBCs are a major source of plasma IL-33.
- IL-33 is produced during RBC maturation.
- RBC hemolysis releases IL-33, potentially contributing to inflammatory responses.
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