Retention of functional mitochondria in mature red blood cells from patients with sickle cell disease.
Retention of functional mitochondria in mature red blood cells from patients with sickle cell disease.
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DOI：
10.1111/bjh.18287
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发表时间：
2022-08
影响因子：
6.5
通讯作者：
Hudson, Krystalyn E.
中科院分区：
文献类型：
--
作者：
Moriconi, Chiara;Dzieciatkowska, Monika;Roy, Micaela;D'Alessandro, Angelo;Roingeard, Philippe;Lee, June Young;Gibb, David R.;Tredicine, Maria;McGill, Marlon A.;Qiu, Annie;La Carpia, Francesca;Francis, Richard O.;Hod, Eldad A.;Thomas, Tiffany;Picard, Martin;Akpan, Imo J.;Luckey, Chance John;Zimring, James C.;Spitalnik, Steven L.;Hudson, Krystalyn E.
镰状细胞病（SCD）是一种遗传性血液病，其特征是镰状红细胞（RBC），对溶血更敏感，并可导致疾病的病理生理学。虽然SCD的治疗可以包括RBC输注，但SCD患者的同种免疫率很高。我们假设SCD患者的红细胞具有功能活跃的线粒体，可以引起1型干扰素反应。我们评估了来自>100名SCD患者的血液样本，发现与健康献血者相比，网织红细胞和成熟红细胞中线粒体的频率升高。成熟红细胞中线粒体的存在通过流式细胞术、电子显微镜和蛋白质组学分析证实。成熟红细胞中的线粒体具有代谢能力，如通过酶活性和升高的红细胞衍生代谢物水平所确定的。RBC中代谢活性线粒体可能增加氧化应激，这可能促进和/或加剧SCD并发症。共同培养的红细胞与嗜中性粒细胞诱导生产1型干扰素，这是已知的增加红细胞同种异体免疫率。这些数据表明，保留在成熟红细胞中的线粒体是功能性的，可以引起免疫反应，这表明红细胞中线粒体的不适当保留可能在SCD并发症中起着未被充分认识的作用，并且是红细胞同种异体免疫的风险因素。
Sickle cell disease (SCD) is an inherited blood disorder characterized by sickled red blood cells (RBCs), which are more sensitive to hemolysis and can contribute to disease pathophysiology. Although treatment of SCD can include RBC transfusion, patients with SCD have high rates of alloimmunization. We hypothesized that RBCs from patients with SCD have functionally active mitochondria and can elicit a type 1 interferon response. We evaluated blood samples from >100 patients with SCD and found elevated frequencies of mitochondria in reticulocytes and mature RBCs, as compared to healthy blood donors. The presence of mitochondria in mature RBCs was confirmed by flow cytometry, electron microscopy, and proteomic analysis. The mitochondria in mature RBCs were metabolically competent, as determined by enzymatic activities and elevated levels of mitochondria-derived metabolites. Metabolically-active mitochondria in RBCs may increase oxidative stress, which could facilitate and/or exacerbate SCD complications. Co-culture of mitochondria-positive RBCs with neutrophils induced production of type 1 interferons, which are known to increase RBC alloimmunization rates. These data demonstrate that mitochondria retained in mature RBCs are functional and can elicit immune responses, suggesting that inappropriate retention of mitochondria in RBCs may play an underappreciated role in SCD complications and be an RBC alloimmunization risk factor.
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影响因子：
10.1
作者：
D'Alessandro A;Fu X;Kanias T;Reisz JA;Culp-Hill R;Guo Y;Gladwin MT;Page G;Kleinman S;Lanteri M;Stone M;Busch MP;Zimring JC;Recipient Epidemiology and Donor Evaluation Study-III (REDS III)
通讯作者：
Recipient Epidemiology and Donor Evaluation Study-III (REDS III)
影响因子：
64.5
作者：
Caielli S;Cardenas J;de Jesus AA;Baisch J;Walters L;Blanck JP;Balasubramanian P;Stagnar C;Ohouo M;Hong S;Nassi L;Stewart K;Fuller J;Gu J;Banchereau JF;Wright T;Goldbach-Mansky R;Pascual V
通讯作者：
Pascual V
影响因子：
7.5
作者：
Gautier, Emilie-Fleur;Leduc, Marjorie;Mayeux, Patrick
通讯作者：
Mayeux, Patrick
影响因子：
2.6
作者：
Jagadeeswaran, Ramasamy;Vazquez, Benjamin A.;Rivers, Angela
通讯作者：
Rivers, Angela
影响因子：
64.8
作者：
Chouchani, Edward T.;Pell, Victoria R.;Gaude, Edoardo;Aksentijevic, Dunja;Sundier, Stephanie Y.;Robb, Ellen L.;Logan, Angela;Nadtochiy, Sergiy M.;Ord, Emily N. J.;Smith, Anthony C.;Eyassu, Filmon;Shirley, Rachel;Hu, Chou-Hui;Dare, Anna J.;James, Andrew M.;Rogatti, Sebastian;Hartley, Richard C.;Eaton, Simon;Costa, Ana S. H.;Brookes, Paul S.;Davidson, Sean M.;Duchen, Michael R.;Saeb-Parsy, Kourosh;Shattock, Michael J.;Robinson, Alan J.;Work, Lorraine M.;Frezza, Christian;Krieg, Thomas;Murphy, Michael P.
通讯作者：
Murphy, Michael P.