Hydroxycarbamide modulates components involved in the regulation of adenosine levels in blood cells from sickle-cell anemia patients

被引:13
作者
Silva-Pinto, Ana C. [1 ,2 ]
Dias-Carlos, Carolina [1 ,2 ]
Saldanha-Araujo, Felipe [3 ]
Ferreira, Flavia I. S. [4 ]
Palma, Patricia V. B. [1 ,2 ]
Araujo, Amelia G. [1 ,2 ]
Queiroz, Regina H. C. [4 ]
Elion, Jacques [5 ]
Covas, Dimas T. [1 ,2 ]
Zago, Marco A. [1 ,2 ]
Panepucci, Rodrigo A. [1 ,2 ]
机构
[1] Univ Sao Paulo, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ctr Cell Therapy CTC, BR-14051140 Sao Paulo, Brazil
[2] Univ Sao Paulo, Reg Blood Ctr, Fac Med FMRP, BR-14051140 Sao Paulo, Brazil
[3] Univ Brasilia UnB, Dept Pharm, Fac Hlth Sci, Brasilia, DF, Brazil
[4] Univ Sao Paulo, Fac Pharmacol Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, Ribeirao Preto, Brazil
[5] Univ Paris Diderot, Unite Mixte Rech UMR INSERM 763, Hop Robert Debre, Paris, France
基金
巴西圣保罗研究基金会;
关键词
Sickle-cell anemia; Hydroxycarbamide; Adenosine; Adenosine deaminase; T regulatory cells; COMBINED IMMUNODEFICIENCY DISEASE; DEAMINASE-DEFICIENT MICE; T-CELLS; A(2A) RECEPTORS; EXTRACELLULAR ADENOSINE; ACTIVATED MONOCYTES; IMMUNE-RESPONSE; DOWN-REGULATION; TISSUE-DAMAGE; HYPOXIA;
D O I
10.1007/s00277-014-2066-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent studies have demonstrated the role of adenosine (ADO) in sickle-cell anemia (SCA). ADO is produced by CD39 and CD73 and converted to inosine by adenosine deaminase (ADA). We evaluated the effects of hydroxycarbamide (HU) treatment on the modulation of adenosine levels in SCA patients. The expressions of CD39, CD73, and CD26 were evaluated by flow cytometry on blood cells in 15 HU-treated and 17 untreated patients and 10 healthy individuals. RNA was extracted from monocytes, and ADA gene expression was quantified by real-time PCR. ADA activity was also evaluated. We found that ADA transcripts were two times higher in monocytes of HU-treated patients, compared with untreated (P = 0.039). Monocytes of HU-treated patients expressed CD26, while monocytes of controls and untreated patients did not (P = 0.023). In treated patients, a lower percentage of T lymphocytes expressed CD39 compared with untreated (P = 0.003), and the percentage of T regulatory (Treg) cells was reduced in the treated group compared with untreated (P = 0.017) and controls (P = 0.0009). Besides, HU-treated patients displayed increased ADA activity, compared with untreated. Our results indicate a novel mechanism of action of HU mediated by the reduction of adenosine levels and its effects on pathophysiological processes in SCA.
引用
收藏
页码:1457 / 1465
页数:9
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