Vignola A M, Riccobono L, Mirabella A, Profita M, Chanez P, Bellia V, Mautino G, D'accardi P, Bousquet J, Bonsignore G
Istituto di Fisiopatologia Respiratoria, Consiglio Nazionale delle Ricerche, Palermo; Istituto di Medicina Generale e Pneumologia, Università di Palermo, Palermo, Italy.
Am J Respir Crit Care Med. 1998 Dec;158(6):1945-50. doi: 10.1164/ajrccm.158.6.9803014.
Asthma and chronic bronchitis are inflammatory diseases with extracellular matrix (ECM) remodeling and collagen deposition. Collagen homeostasis is controlled by metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated MMP and TIMP balance in induced sputum of 10 control, 31 untreated asthmatic, and 16 chronic bronchitic subjects. We first performed zymographic analysis to identify the profile of MMPs. Zymography revealed a similar MMPs profile in all populations studied and that MMP-9 was the major enzyme released. We then measured, using enzyme immunoassay, the concentrations of MMP-9 and of its inhibitor TIMP-1 and evaluated whether airflow limitation may be associated with an imbalance between these enzymes. MMP-9 and TIMP-1 concentrations were greater in sputum of patients with asthma and chronic bronchitis than in control subjects. The molar ratio between MMP-9 and TIMP-1 was lower in asthmatics and chronic bronchitics than in control subjects, and positively correlated with FEV1 values. In asthma, MMP-9 levels were significantly correlated with the number of macrophages and neutrophils. This study shows that airway inflammation in asthma and chronic bronchitis is associated with an imbalance between MMP-9 and TIMP-1 which may have a role in the pathogenesis of ECM remodeling and airflow obstruction.
哮喘和慢性支气管炎是伴有细胞外基质（ECM）重塑和胶原蛋白沉积的炎症性疾病。胶原蛋白稳态由金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）控制。我们评估了10名对照者、31名未经治疗的哮喘患者和16名慢性支气管炎患者诱导痰中的MMP和TIMP平衡。我们首先进行酶谱分析以确定MMPs的谱型。酶谱分析显示，在所有研究人群中MMPs谱型相似，且MMP-9是释放的主要酶。然后，我们使用酶免疫测定法测量了MMP-9及其抑制剂TIMP-1的浓度，并评估气流受限是否可能与这些酶之间的失衡有关。哮喘和慢性支气管炎患者痰液中MMP-9和TIMP-1的浓度高于对照者。哮喘患者和慢性支气管炎患者中MMP-9与TIMP-1的摩尔比低于对照者，且与第一秒用力呼气容积（FEV1）值呈正相关。在哮喘中，MMP-9水平与巨噬细胞和中性粒细胞的数量显著相关。这项研究表明，哮喘和慢性支气管炎中的气道炎症与MMP-9和TIMP-1之间的失衡有关，这可能在ECM重塑和气流阻塞的发病机制中起作用。
