Red Blood Cells Store and Release Interleukin-33.
Red Blood Cells Store and Release Interleukin-33.
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DOI：
10.1097/jim.0000000000000213
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Zhao Y
中科院分区：
文献类型：
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作者：
Wei J;Zhao J;Schrott V;Zhang Y;Gladwin M;Bullock G;Zhao Y
白介素33(IL-33)是IL-1细胞因子超家族中的一员，能有效地驱动多种细胞因子的产生，并在炎症性疾病的发病机制中起作用。IL-33是一种核蛋白，从凋亡或坏死的细胞中释放出来。血清IL-33水平在各种疾病中升高，如特应性皮炎、慢性丙型肝炎感染和哮喘。在这里，我们表明红细胞(RBC)是血浆IL-33的主要来源之一。裂解红细胞培养上清液中IL-33水平显著升高。溶血时血浆IL-33水平升高，且与溶血程度呈正相关。体外培养的原代人红系祖细胞在分化后期检测到IL-33蛋白和mRNA的表达，提示IL-33在红细胞成熟过程中表达。此外，去血红蛋白的红细胞裂解物可诱导人上皮细胞表达IL-8。这种作用在表达IL-33诱骗受体的细胞中减弱，在表达IL-33受体的细胞中增强。这些结果表明，红系祖细胞产生IL-33，循环中的红细胞是溶血时释放的IL-33的主要来源。
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. 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. 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. IL-33 protein and mRNA 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.