Regulation of antiprotease and antimicrobial protein secretion by airway submucosal gland serous cells
Regulation of antiprotease and antimicrobial protein secretion by airway submucosal gland serous cells
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DOI：
10.1074/jbc.m407077200
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发表时间：
2004-09-10
影响因子：
4.8
通讯作者：
Wine, JJ
中科院分区：
文献类型：
--
作者：
Joo, NS;Lee, DJ;Wine, JJ
气道粘膜下腺浆液细胞表达囊性纤维化跨膜传导调节因子（CFTR）并分泌抗菌、抗炎和抗氧化分子。在囊性纤维化中，腺体分泌减少可能损害先天气道宿主防御。我们使用Calu-3细胞作为浆液细胞模型来研究释放的蛋白质类型，释放它们的途径，以及CFTR活性在蛋白质释放中的可能参与。许多蛋白质组成性地分泌到根尖液中，并显示出对激动剂的释放增加。我们通过高压液相色谱-质谱法和逆转录酶PCR鉴定了其中的一些，包括溶菌酶，铁苷酸（蛋白质NGAL），通过结合含铁铁载体抑制细菌生长，HSC-71，被认为具有抗炎特性，以及丝氨酸蛋白酶抑制剂α -1-抗胰蛋白酶和α -1-抗凝乳胰蛋白酶。它可能具有抗菌剂的功能，并在减少丝氨酸蛋白酶对上皮Na+通道的激活方面发挥潜在作用。我们使用酶联免疫吸附法定量Calu-3细胞对各种激动剂和抑制剂的溶菌酶分泌。Forskolin使溶菌酶分泌率（J(lyz)）从32 ng/hr/cm(2)提高到77 ng/hr/cm(n=36, p
Airway submucosal gland serous cells express the cystic fibrosis transmembrane conductance regulator (CFTR) and secrete antimicrobial, anti-inflammatory, and antioxidant molecules. In cystic fibrosis, diminished gland secretion may impair innate airway host defenses. We used Calu-3 cells as a serous cell model to study the types of proteins released, the pathways that release them, and the possible involvement of CFTR activity in protein release. Many proteins were secreted constitutively into the apical fluid and showed increased release to agonists. We identified some of them by high pressure liquid chromatography-mass spectrometry and reverse transcriptase PCR, including lysozyme, siderocalin (the protein NGAL), which inhibits bacterial growth by binding iron-containing siderophores, HSC-71, which is thought to have anti-inflammatory properties, and the serine protease inhibitors alpha-1-antitrypsin and alpha-1-antichymotrypsin, which may function as antimicrobials as well as play a potential role in diminishing the activation of epithelial Na+ channels by serine proteases. We used an enzyme-linked immunosorbent assay to quantify lysozyme secretion by Calu-3 cells in response to various agonists and inhibitors. Forskolin increased the lysozyme secretion rate (J(lyz)) from 32 to 77 ng/hr/cm(2) (n=36, p