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不确定型恰加斯病患者淋巴细胞中的E-NTPD酶和E-ADA活性发生改变。

E-NTPDase and E-ADA activities are altered in lymphocytes of patients with indeterminate form of Chagas' disease.

作者信息

Souza Viviane do Carmo Gonçalves, Schlemmer Karine Bizzi, Noal Cristiano Bicca, Jaques Jeandre Augusto dos Santos, Zimmermann Carine Eloise Prestes, Leal Cláudio Alberto Martins, Fleck Juliana, Casali Emerson Andre, Morsch Vera Maria, Schetinger Maria Rosa Chitolina, Leal Daniela Bitencourt Rosa

机构信息

Departamento de Microbiologia e Parasitologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Av. Roraima, 97105-900, Santa Maria, RS, Brazil.

出版信息

Parasitol Int. 2012 Dec;61(4):690-6. doi: 10.1016/j.parint.2012.07.008. Epub 2012 Jul 27.

Abstract

Trypanosoma cruzi infection triggers a chronic inflammatory process in human host and purinergic system ecto-enzymes play an important role in modulating the inflammatory and immune responses. In this study, it was investigated ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase; EC 3.6.1.5; CD39) and ecto-adenosine deaminase (E-ADA; EC 3.5.4.4) activities in lymphocytes from patients with indeterminate form of Chagas' disease (IFCD). Twenty-five IFCD patients and 25 healthy subjects (control group) were selected. The peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Adenine nucleotides and adenosine levels were determined in serum by HPLC and the E-NTPDase1 expression in lymphocytes by Western blot analysis. E-NTPDase (ATP and ADP as substrates) and E-ADA (adenosine as substrate) activities were decreased in lymphocytes from IFCD patients (P<0.05 and P<0.01, respectively), while the E-NTPDase1 expression presented no changes in these patients. Serum ATP levels showed to be decreased (P<0.05) and both AMP (P<0.01) and adenosine (P<0.001) levels were increased in the IFCD group. The enzymatic alterations observed are in agreement with the immune response against T. cruzi infection in IFCD patients, since the decreased extracellular ATP and the increased adenosine levels trigger a Th2 anti-inflammatory response, which it is associated to adaptation of host to parasite, preventing clinical progress of disease.

摘要

克氏锥虫感染会在人类宿主中引发慢性炎症过程,嘌呤能系统外切酶在调节炎症和免疫反应中起重要作用。在本研究中,对查加斯病不确定型(IFCD)患者淋巴细胞中的外切核苷三磷酸二磷酸水解酶(E-NTPDase;EC 3.6.1.5;CD39)和外切腺苷脱氨酶(E-ADA;EC 3.5.4.4)活性进行了研究。选取了25例IFCD患者和25名健康受试者(对照组)。分离外周淋巴细胞并测定E-NTPDase和E-ADA活性。通过高效液相色谱法测定血清中的腺嘌呤核苷酸和腺苷水平,并通过蛋白质印迹分析测定淋巴细胞中E-NTPDase1的表达。IFCD患者淋巴细胞中的E-NTPDase(以ATP和ADP为底物)和E-ADA(以腺苷为底物)活性降低(分别为P<0.05和P<0.01),而这些患者的E-NTPDase1表达无变化。IFCD组血清ATP水平降低(P<0.05),AMP(P<0.01)和腺苷(P<0.001)水平均升高。观察到的酶学改变与IFCD患者针对克氏锥虫感染的免疫反应一致,因为细胞外ATP降低和腺苷水平升高会引发Th2抗炎反应,这与宿主对寄生虫的适应性相关,可防止疾病的临床进展。

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