Contribution of 92 kDa gelatinase type IV collagenase in bronchial inflammation during status asthmaticus
Contribution of 92 kDa gelatinase type IV collagenase in bronchial inflammation during status asthmaticus
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DOI：
10.1164/ajrccm.159.4.9708080
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发表时间：
1999-04-01
影响因子：
24.7
通讯作者：
Lafuma, C
中科院分区：
文献类型：
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作者：
Lemjabbar, H;Gosset, P;Lafuma, C
为了评估与轻度哮喘相比，严重哮喘的炎症特征，我们研究了6例哮喘持续状态（SA）接受机械通气（MV）的患者和6例轻度哮喘患者的支气管灌洗液中92 kDa明胶酶基质金属蛋白酶（MMP-9）的分泌。10名健康的非通气患者和4名患者下MV没有预先存在的呼吸系统疾病也进行了调查。SA患者的特征是明显的嗜酸性炎症（82 +/- 4% vs轻度哮喘10%）。在酶和免疫分析的基础上，结果显示，SA患者的上皮衬里液（ELF）中92 kDa明胶酶（MMP-9）浓度急剧增加10- 160倍，（46和26 kDa）的溶基质素-1基质金属蛋白酶（MMP-3）和可检测浓度的游离金属胶原蛋白溶解活性（1-5 μ g水解明胶/48小时/ml ELF）。伴随的金属蛋白酶组织抑制剂-1（TIMP-1）水平升高仅在SA患者中显示，从而至少部分抵消了过量的活化92 kDa明胶酶。仅在SA患者中观察到白蛋白水平急性增强;此外，Tn、92 kDa明胶酶和白蛋白水平显著正相关（r = 0.96，p < 0.0007），表明92 kDa明胶酶可能是SA患者支气管通透性增加的原因。有几个论点支持：SA期间的92 kDa明胶酶来源于大量活化的化学吸引的中性粒细胞和响应于原位肺损伤的活化的支气管上皮细胞。在轻度哮喘期间未观察到ELF、白蛋白、MMP-9、MMP-3、TIMP-1或层粘连蛋白降解产物的相关变化，这一事实强烈支持SA中的气道炎症机制与轻度哮喘中观察到的机制完全不同。
In order to assess inflammatory features related to severe asthma as compared with mild asthma, we investigated the secretion of 92 kDa gelatinase matrix metalloproteinase (MMP-9) in bronchial lavages of six patients undergoing mechanical ventilation (MV) for status asthmaticus (SA) and in six patients with mild asthma. Ten healthy nonventilated patients and four patients under MV without preexisting respiratory disease were also investigated. Patients with SA were characterized by prominent neutrophilic inflammation (82 +/- 4% versus 10% in mild asthma). On the basis of enzymatic and immunological analysis, results showed an acute 10- to 160-fold increase of 92 kDa gelatinase (MMP-9) concentration in epithelial lining fluid (ELF) from patients with SA together with activated forms (46 and 26 kDa) of stromelysin-1 matrix metalloproteinase (MMP-3) and detectable concentration of free metallogelatinolytic activity (1-5 mu g gelatin hydrolyzed/48 h/ml ELF). Concomitant elevated level of tissue inhibitor of metalloproleinase-1 (TIMP-1) was shown only in patients with SA, thus counterbalancing, at least partially, excess of activated 92 kDa gelatinase. Acutely enhanced albumin levels were only observed in patients with SA; Tn addition, 92 kDa gelatinase and albumin levels were significantly and positively correlated (r = 0.96, p < 0.0007), suggesting that 92 kDa gelatinase may account for increased bronchial permeability in patients with SA. Several arguments support: that 92 kDa gelatinase during SA originates both from numerous activated chemoattracted neutrophils and from activated bronchial epithelial cells in response to in situ lung injury. The fact that no relevant change In ELF, albumin, MMP-9, MMP-3, TIMP-1, or laminin degradation products was observed during mild asthma, strongly supports that the mechanism of airway inflammation in SA is quite distinct from that observed in mild asthma.