Montaño L M, Vargas M H, Díaz-Hernández V, De Ita M, Kazakova R, Barajas-López C
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México DF, México.
Departamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias, México DF, México.
Allergy. 2016 Jan;71(1):124-8. doi: 10.1111/all.12772. Epub 2015 Oct 20.
Several studies suggest that ATP and related nucleotides play a role in the pathophysiology of asthma. However, the functionality of ectonucleotidases in this disease has been scantly investigated. We studied total ectonucleotidase activity in leukocytes from patients suffering from asthma exacerbation and explored the expression of E-NTPDase 1, 2, 3, and 8, and E-NPP1, 2, and 3, in their polymorphonuclear cells by immunofluorescence and qPCR. Leukocytes from patients with mild or moderate asthma exacerbation had similar ectonucleotidase activity than leukocytes from healthy subjects, while in patients with severe asthma exacerbation, this activity was lower. Of the ectonucleotidases studied, only E-NPP1 displayed diminished immunofluorescence and a significant decrease in its mRNA expression, both in patients with severe asthma exacerbation. This reduced E-NPP1 expression could be responsible for increased amounts of ATP or other nucleotides, capable of worsening asthma exacerbation, and warranting further investigation.
多项研究表明,三磷酸腺苷(ATP)及相关核苷酸在哮喘的病理生理学中发挥作用。然而,核苷酸外切酶在该疾病中的功能鲜有研究。我们研究了哮喘急性加重期患者白细胞中的总核苷酸外切酶活性,并通过免疫荧光和定量聚合酶链反应(qPCR)探究了其多形核细胞中E-NTPDase 1、2、3和8以及E-NPP1、2和3的表达。轻度或中度哮喘急性加重期患者的白细胞与健康受试者的白细胞具有相似的核苷酸外切酶活性,而重度哮喘急性加重期患者的这种活性较低。在所研究的核苷酸外切酶中,只有E-NPP1在重度哮喘急性加重期患者中显示出免疫荧光减弱且其mRNA表达显著降低。E-NPP1表达的降低可能导致ATP或其他核苷酸量增加,从而加重哮喘急性加重,值得进一步研究。