High expression of pulmonary proteinase-activated receptor 2 in acute and chronic lung injury in preterm infants
High expression of pulmonary proteinase-activated receptor 2 in acute and chronic lung injury in preterm infants
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DOI：
10.1203/01.pdr.0000161416.63314.70
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发表时间：
2005-06-01
影响因子：
3.6
通讯作者：
Andersson, S
中科院分区：
文献类型：
--
作者：
Cederqvist, K;Haglund, C;Andersson, S
蛋白酶激活受体2（PAR 2）是一种由丝氨酸蛋白酶（如胰蛋白酶）激活的G蛋白偶联受体，在炎症和纤维增生过程中起重要作用。在早产儿中，支气管肺发育不良（BPD）的发展以早期肺部炎症和随后的间质纤维化为特征。高肺胰蛋白酶-2已被证明与BPD的发展有关。我们通过免疫组织化学方法研究了PAR 2和胰蛋白酶-2在胎儿尸检肺标本（n = 10）、死于急性或长期呼吸窘迫综合征（RDS）（n = 8和n = 7）或BPD（n = 6）的早产儿尸检肺标本（n = 10）和作为对照的无肺病新生儿尸检肺标本（n = 5）中的表达和分布。与无肺病理改变的婴儿相比，在长期RDS和BPD中，支气管上皮中PAR（2）免疫反应性显著升高（分别为p < 0.05和p < 0.005）。在肺泡上皮中，PAR_i的表达在RDS延长的新生儿中比无肺病理的新生儿高（p < 0.05）。此外，PAR在延长RDS或BPD的增厚和纤维化肺泡壁的肌成纤维细胞中检测到强表达。胰蛋白酶-2与PAR（2）共定位于支气管肺泡上皮。这些结果提示PAR（2）可能被胰蛋白酶-2激活，参与了与早产儿RDS向BPD进展相关的炎症和纤维增生。
Proteinase-activated receptor 2 (PAR2), a G-protein-coupled receptor activated by serine proteinases such as trypsin, has been suggested to play an important role in inflammatory and fibro-proliferative processes. In preterm infants, the development of bronchopulmonary dysplasia (BPD) is characterized by early pulmonary inflammation and subsequent interstitial fibrosis. High pulmonary trypsin-2 has been shown to be associated with the development of BPD. We studied the expression and distribution of PAR2 and trypsin-2 by immunohistochemistry in autopsy lung specimens of fetuses (n = 10), of preterm infants who died of acute or prolonged respiratory distress syndrome (RDS) (n = 8 and n = 7, respectively) or BPD (n = 6), and of newborn infants without lung disease (n = 5) who served as controls. In prolonged RDS and BPD, PAR(2) immunoreactivity was significantly higher in bronchial epithelium when compared with infants without pulmonary pathology (p < 0.05 and p < 0.005, respectively). In alveolar epithelium, expression of PAR, was elevated in prolonged RDS when compared with newborn infants without pulmonary pathology (p < 0.05). Moreover, strong expression of PAR, was detected in myofibroblasts of thickened and fibrotic alveolar walls in prolonged RDS or BPD. Trypsin-2 was co-localized with PAR(2) in bronchoalveolar epithelium. These findings suggest that PAR(2) possibly activated by trypsin-2, may participate in inflammation and fibroproliferation associated with progression of RDS toward BPD in preterm infants.