Identification of Epithelial Phospholipase A2 Receptor 1 as a Potential Target in Asthma.
Identification of Epithelial Phospholipase A2 Receptor 1 as a Potential Target in Asthma.
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DOI：
10.1165/rcmb.2015-0150oc
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发表时间：
2016-12
影响因子：
6.4
通讯作者：
J. Nolin;H. Ogden;Y. Lai;W. Altemeier;C. Frevert;James G. Bollinger;Gajendra S. Naika;A. Kicic;S. Stick;G. Lambeau;W. Henderson;M. Gelb;T. Hallstrand
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文献类型：
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作者：
J. Nolin;H. Ogden;Y. Lai;W. Altemeier;C. Frevert;James G. Bollinger;Gajendra S. Naika;A. Kicic;S. Stick;G. Lambeau;W. Henderson;M. Gelb;T. Hallstrand
分泌型磷脂酶A2（sPLA 2）调节类花生酸的形成，并与哮喘有关。虽然sPLA 2作为酶发挥作用，但一些sPLA 2以高亲和力结合C型凝集素受体，称为PLA 2 R1，其在细胞信号传导和sPLA 2清除中具有功能。我们试图研究PLA 2 R1在哮喘患者气道上皮中的表达，以及小鼠PLA 2 R1基因在哮喘模型中的功能。通过微阵列和定量PCR评估了两个不同队列的哮喘儿童上皮刷拭中PLA 2 R1的表达，并对成人哮喘患者的支气管内组织和上皮刷拭进行了PLA 2 R1的免疫染色。在过敏性哮喘的卵清蛋白（OVA）模型中表征Pla 2 r1（Pla 2 r1-/-）缺陷的C57 BL/129小鼠。PLA 2 R1在两组过敏性哮喘儿童的上皮刷毛中差异性过表达。支气管内膜组织中PLA 2 R1的免疫染色定位于粘膜下腺上皮和柱状上皮细胞。OVA致敏和激发后，Pla 2 r1-/-小鼠气道高反应性增加，嗜酸性粒细胞向支气管周围空间和支气管肺泡灌洗液的细胞运输增加，气道通透性增加。此外，Pla 2 r1-/-小鼠在肺中有更多的树突状细胞，更高水平的OVA特异性IgG，并增加肺白细胞产生的1型和2型细胞因子。PLA 2 R1在哮喘的气道上皮中增加，并作为气道高反应性、气道渗透性、抗原致敏和气道炎症的调节剂。
Secreted phospholipase A2s (sPLA2s) regulate eicosanoid formation and have been implicated in asthma. Although sPLA2s function as enzymes, some of the sPLA2s bind with high affinity to a C-type lectin receptor, called PLA2R1, which has functions in both cellular signaling and clearance of sPLA2s. We sought to examine the expression of PLA2R1 in the airway epithelium of human subjects with asthma and the function of the murine Pla2r1 gene in a model of asthma. Expression of PLA2R1 in epithelial brushings was assessed in two distinct cohorts of children with asthma by microarray and quantitative PCR, and immunostaining for PLA2R1 was conducted on endobronchial tissue and epithelial brushings from adults with asthma. C57BL/129 mice deficient in Pla2r1 (Pla2r1-/-) were characterized in an ovalbumin (OVA) model of allergic asthma. PLA2R1 was differentially overexpressed in epithelial brushings of children with atopic asthma in both cohorts. Immunostaining for PLA2R1 in endobronchial tissue localized to submucosal glandular epithelium and columnar epithelial cells. After OVA sensitization and challenge, Pla2r1-/- mice had increased airway hyperresponsiveness, as well as an increase in cellular trafficking of eosinophils to the peribronchial space and bronchoalveolar lavage fluid, and an increase in airway permeability. In addition, Pla2r1-/- mice had more dendritic cells in the lung, higher levels of OVA-specific IgG, and increased production of both type-1 and type-2 cytokines by lung leukocytes. PLA2R1 is increased in the airway epithelium in asthma, and serves as a regulator of airway hyperresponsiveness, airway permeability, antigen sensitization, and airway inflammation.