title: Red Blood Cells Store and Release Interleukin-33.
abstract: Interleukin-33 (IL-33) is a member of the IL-1 cytokine superfamily that potently drives production of a variety of cytokines and contributes to the pathogenesis of inflammatory diseases. The IL-33 is a nuclear protein and is released from apoptotic or necrotic cells. Serum IL-33 levels are increased in various diseases, such as atopic dermatitis, chronic hepatitis C infection, and asthma. Here, we show that red blood cells (RBCs) are one of the major sources of plasma IL-33. The IL-33 levels are significantly increased in supernatants from lysed RBCs. Plasma IL-33 levels are increased in patients during hemolysis, and plasma IL-33 levels show a positive correlation with degree of hemolysis. The IL-33 protein and messenger RNA levels were detected in the late stages of differentiation in ex vivo primary human erythroid progenitor cell cultures, suggesting that IL-33 is expressed during maturation of RBCs. Furthermore, hemoglobin depleted red cell lysates induced IL-8 expression in human epithelial cells. This effect was attenuated in IL-33 decoy receptor expressing cells and was enhanced in IL-33 receptor expressing cells. These results suggest that erythroid progenitor cells produce IL-33 and circulating RBCs represent a major source of IL-33 that is released upon hemolysis.
authors.affiliation: From *Department of Medicine, †Acute Lung Injury Center of Excellence, ‡Vascular Medicine Institute, §Department of Pathology, and ∥Department of Cell Biology, University of Pittsburgh, PA.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Valerie
authors.initials: V
authors.lastname: Schrott
authors.forename: Yingze
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Gladwin
authors.forename: Grant
authors.initials: G
authors.lastname: Bullock
authors.forename: Yutong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood; D002457:Cell Extracts; D004847:Epithelial Cells / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D002457:Cell Extracts; D006454:Hemoglobins; D000067596:Interleukin-33; D016209:Interleukin-8; D012333:RNA, Messenger