Increased release of matrix metalloproteinase-9 in bronchoalveolar lavage fluid and by alveolar macrophages of asthmatics
Increased release of matrix metalloproteinase-9 in bronchoalveolar lavage fluid and by alveolar macrophages of asthmatics
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DOI：
10.1165/ajrcmb.17.5.2562
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发表时间：
1997-11-01
影响因子：
6.4
通讯作者：
Capony, F
中科院分区：
文献类型：
--
作者：
Mautino, G;Oliver, N;Capony, F
为探讨基质金属蛋白酶(MMPs)在哮喘炎症中的作用，我们在短期培养条件下检测了BAL液中MMPs的释放及肺泡巨噬细胞(AM)对MMPs的产生和调节。BAL来自38名哮喘患者(24名未经治疗，14名接受吸入皮质类固醇治疗)，26名健康非吸烟者，18名慢性支气管炎患者作为另一炎症的对照组。通过酶谱分析，发现BAL液和AM上清液中存在的MMPs在所有种群中的分布是相似的。释放的主要酶经免疫学鉴定为基质金属蛋白酶-9，一种有效的胶原酶和弹性分解酶。用酶免疫测定法测定，与其他人群相比，它在液体中的释放显著增加，在未经治疗的哮喘患者的AM上清液中显著增加。哮喘患者的高水平的基质金属蛋白酶-9不能用AM对白介素4、干扰素-伽马或地塞米松的不同敏感性来解释，这些化合物已被证明能抑制基质金属蛋白酶-9。蛋白激酶C(PKC)激活剂佛波酯佛波酯(PMA)可显著增加健康对照组AM中的基质金属蛋白酶-9(MMP9)，但对未经治疗的哮喘患者无明显影响。PKC抑制剂Calphostin C和H7显著减少PMA刺激的健康受试者AM和未经治疗的哮喘患者AM自发释放的MMP-9。PKA抑制剂H8在这两个群体中都不活跃。这些数据表明，未经治疗的哮喘患者AM中释放的基质金属蛋白酶-9的刺激，至少部分是通过激活PKC的信号来实现的。
In order to determine whether matrix metalloproteinases (MMPs) contribute to inflammation in asthma, we have examined the release of MMPs in bronchoalveolar lavage (BAL) fluids and their production and regulation by alveolar macrophages (AM), in short-term culture. BAL was collected from 38 asthmatic subjects (24 untreated and 14 treated with inhaled corticosteroids), 26 healthy nonsmokers, and 18 patients with chronic bronchitis used as a control group for another inflammation. The profile of MMPs present in BAL fluid and AM supernatant, determined by zymographic analysis, was found to be similar in all populations. The main enzyme released was identified immunologically as MMP-9, a potent collagenolytic and elastolytic enzyme. Its release, measured using enzyme immunoassay, was significantly enhanced in fluids :and in AM supernatants from untreated asthmatics compared with those from the other populations. Enhanced MMP-9 levels, in asthma, could not be explained by a different sensitivity of AM to interleukin-4, interferon-gamma, or dexamethasone, compounds that have been shown to inhibit MMP-9. The phorbol ester phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, significantly increased MMP-9 in AM from healthy control subjects but not in those from untreated asthmatics. Calphostin C and H7, PKC inhibitors, significantly reduced PMA-stimulated MMP-9 release in AM from healthy control subjects and spontaneous MMP-9 release in AM from untreated asthmatics. H8, a PKA inhibitor, was inactive in both populations. These data suggest that the stimulation of MMP-9 release in AM from untreated asthmatic patients occurs, at least partly, via signals activating PKC.