Use of MMP-8 and MMP-9 to assess disease severity in children with viral lower respiratory tract infections
Use of MMP-8 and MMP-9 to assess disease severity in children with viral lower respiratory tract infections
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DOI：
10.1002/jmv.23301
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发表时间：
2012-09-01
影响因子：
12.7
通讯作者：
Hermans, Peter W. M.
中科院分区：
文献类型：
--
作者：
Brand, Kim H.;Ahout, Inge M. L.;Hermans, Peter W. M.
基质金属蛋白酶（matrix metalloproteinases，MMPs）在哮喘、慢性阻塞性肺疾病等呼吸道炎症性疾病中发挥重要作用。有假设认为，MMP-8和MMP-9可能作为生物标志物，以评估疾病的严重程度，在病毒性下呼吸道感染的儿童。采用实时荧光定量PCR法检测了153例轻、中、重度病毒性下呼吸道感染患儿急性期和恢复期外周血单个核细胞（PBMC）和粒细胞中MMP-8和MMP-9 mRNA的表达水平。此外，MMP-8和MMP-9浓度在血液和鼻咽标本中测定急性轻度，中度和重度感染，并在恢复后使用ELISA。此外，在体外用RSV、LPS（TLR 4激动剂）和Pam 3Cys（TLR 2激动剂）刺激从健康志愿者获得的PBMC和嗜中性粒细胞。儿童病毒性下呼吸道感染的疾病严重程度与PBMC和粒细胞中MMP-8和MMP-9基因表达水平升高相关。相反，体外实验表明，MMP-8和MMP-9的mRNA和蛋白质的表达在PBMC和粒细胞是不诱导与RSV刺激，最常见的检测病毒在幼儿病毒性下呼吸道感染。这些数据表明PBMC和中性粒细胞中MMP-8和MMP-9基因的表达水平与病毒性下呼吸道感染疾病的严重程度相关。这些观察结果证明了MMP-8和MMP-9作为病毒性呼吸道感染疾病严重程度的潜在标志物的有用性的独立前瞻性研究队列中的未来验证。医学病毒学杂志84：1471-1480，2012. (c)2012 Wiley Periodicals，Inc.
Matrix metalloproteinases (MMPs) play an important role in respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease. It was hypothesized that MMP-8 and MMP-9 may function as biological markers to assess disease severity in viral lower respiratory tract infections in children. MMP-8 and MMP-9 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) and granulocytes obtained in both the acute and recovery phase from 153 children with mild, moderate, and severe viral lower respiratory tract infections were determined using real-time PCR. In addition, MMP-8 and MMP-9 concentrations in blood and nasopharyngeal specimens were determined during acute mild, moderate, and severe infection, and after recovery using ELISA. Furthermore, PBMCs and neutrophils obtained from healthy volunteers were stimulated with RSV, LPS (TLR4 agonist), and Pam3Cys (TLR2 agonist) in vitro. Disease severity of viral lower respiratory tract infections in children is associated with increased expression levels of the MMP-8 and MMP-9 genes in both PBMCs and granulocytes. On the contrary, in vitro experiments showed that MMP-8 and MMP-9 mRNA and protein expression in PBMCs and granulocytes is not induced by stimulation with RSV, the most frequent detected virus in young children with viral lower respiratory tract infections. These data indicate that expression levels of the MMP-8 and MMP-9 genes in both PBMCs and neutrophils are associated with viral lower respiratory tract infections disease severity. These observations justify future validation in independent prospective study cohorts of the usefulness of MMP-8 and MMP-9 as potential markers for disease severity in viral respiratory infections. J. Med. Virol. 84:1471-1480, 2012. (c) 2012 Wiley Periodicals, Inc.