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Epithelial-mesenchymal transition and membrane microparticles: Potential implications for bronchiolitis obliterans syndrome after lung transplantation.
Transplant Immunology ( IF 1.5 ) Pub Date : 2020-02-22 , DOI: 10.1016/j.trim.2020.101273
Benjamin Renaud-Picard 1 , Kevin Vallière 2 , Justine Toussaint 2 , Guillaume Kreutter 2 , Ali El-Habhab 2 , Mohamad Kassem 2 , Fatiha El-Ghazouani 2 , Anne Olland 3 , Sandrine Hirschi 4 , Michele Porzio 4 , Marie-Pierrette Chenard 5 , Florence Toti 2 , Laurence Kessler 6 , Romain Kessler 1
Affiliation  

Long term survival post lung transplantation (LTx) is limited by the occurrence of bronchiolitis obliterans syndrome (BOS). One mechanism involved is the epithelial-mesenchymal transition (EMT). Membrane microparticles (MPs) are known to be involved in some respiratory diseases and in other organs allograft rejection episodes. We hypothesized that leukocyte-derived MPs likely contribute to EMT. To emphasize this physiological concept, our objectives were to: (1) confirm the presence of EMT on explanted lungs from patients who underwent a second LTx for BOS; 2) characterize circulating MPs in transplanted patients, with or without BOS; (3) evaluate in vitro the effect of monocyte-derived MPs in EMT of human bronchial epithelial cells. Our IHC analysis on explanted graft lungs revealed significant pathological signs of EMT with an inhomogeneous destruction of the bronchial epithelium, with decreased expression of the epithelial protein E-cadherin and increased expression of the mesenchymal protein Vimentin. The immunophenotyping of MPs demonstrated that the concentration of MPs carrying E-cadherin was lower in patients affected by BOS (p = .007). In vitro, monocyte-derived MPs produced with LPS were associated with decreased E-cadherin expression (p < .05) along with significant morphological and functional cell modifications. MPs may play a role in EMT onset in bronchial epithelium following LTx.



中文翻译:

上皮-间质转化和膜微粒:肺移植后对闭塞性细支气管炎综合征的潜在影响。

肺移植闭塞症候群(BOS)的发生限制了肺移植(LTx)后的长期生存。涉及的一种机制是上皮-间质转化(EMT)。膜微粒(MPs)已知与某些呼吸系统疾病和同种异体移植排斥反应有关。我们假设白细胞衍生的MP可能有助于EMT。为了强调这一生理学概念,我们的目标是:(1)确认接受第二次LTx BOS治疗的患者的移植肺中是否存在EMT;2)表征有或没有BOS的移植患者中的循环MPs;(3)体外评价单核细胞衍生MPs在人支气管上皮细胞EMT中的作用 我们对移植的移植肺的IHC分析显示,EMT具有明显的病理征象,支气管上皮细胞不均匀破坏,上皮蛋白E-钙黏着蛋白表达降低,间充质蛋白波形蛋白表达增加。MPs的免疫表型表明,受BOS影响的患者中携带E-钙粘蛋白的MPs浓度较低(p  = .007)。在体外,LPS产生的单核细胞衍生的MP与E-钙粘蛋白表达降低(p  <.05)以及显着的形态和功能性细胞修饰有关。MPs可能在LTx后支气管上皮的EMT发作中起作用。

更新日期:2020-02-22
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