Belleguic C, Corbel M, Germain N, Léna H, Boichot E, Delaval P H, Lagente V
INSERM U 456, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 2 avenue du Prof. Léon Bernard, 35043 Rennes cedex, France.
Clin Exp Allergy. 2002 Feb;32(2):217-23. doi: 10.1046/j.1365-2222.2002.01219.x.
Matrix metalloproteinases (MMPs) are likely to be relevant mediators of the extracellular matrix (ECM) degradation and airway remodelling.
We have compared the levels of MMPs, eotaxin and soluble interleukin 2 receptor (IL-2R) in the plasma of healthy subjects, atopic patients and asthmatic patients.
The asthmatic patients were separated into two groups, either well controlled on inhaled therapy or acute severe asthma. Patients with acute severe disease had all received systemic corticosteroids from 12 to 48 h before the blood was taken. Blood was recovered in EDTA tubes, incubated with either f MLP, PMA or vehicle for 10 min and centrifuged. MMP-9, TIMP-1, IL-2R and eotaxin levels were measured in the plasma by ELISA. Moreover, the activity of MMPs was also evaluated by zymography.
An increased basal level of MMP-9 and IL2-R was observed in acute severe asthma. Following stimulation with f MLP and PMA there was an enhanced production of MMP-9 in the plasma of all groups of patients. However, the MMP-9 level was significantly enhanced in acute severe asthma, compared with the others. No difference was found for the TIMP-1 level between the patients. The eotaxin level in plasma was found to be significantly lower in acute severe asthmatics compared with the others groups. Zymography technique showed a significant increased activity of MMP-9 (92 kDa) but not MMP-2 (66 kDa) in the plasma of patients with acute asthma.
The increased in MMP-9 production and activity observed in the present study suggests a process of extracellular matrix degradation in acute severe asthmatic patients and proposes MMP-9 as a non-invasive systemic marker of inflammation and airway remodelling in asthma.
基质金属蛋白酶（MMPs）可能是细胞外基质（ECM）降解和气道重塑的相关介质。
我们比较了健康受试者、特应性患者和哮喘患者血浆中MMPs、嗜酸性粒细胞趋化因子和可溶性白细胞介素2受体（IL-2R）的水平。
将哮喘患者分为两组，一组通过吸入疗法得到良好控制，另一组为急性重症哮喘。急性重症疾病患者在采血前12至48小时均接受了全身皮质类固醇治疗。血液收集于乙二胺四乙酸（EDTA）管中，分别与甲酰甲硫氨酸-亮氨酸-苯丙氨酸（fMLP）、佛波酯（PMA）或赋形剂孵育10分钟后离心。采用酶联免疫吸附测定（ELISA）法测定血浆中MMP-9、基质金属蛋白酶组织抑制因子-1（TIMP-1）、IL-2R和嗜酸性粒细胞趋化因子的水平。此外，还通过酶谱法评估了MMPs的活性。
在急性重症哮喘中观察到MMP-9和IL-2R的基础水平升高。用fMLP和PMA刺激后，所有患者组血浆中MMP-9的产生均增加。然而，与其他组相比，急性重症哮喘中MMP-9水平显著升高。患者之间TIMP-1水平未发现差异。发现急性重症哮喘患者血浆中的嗜酸性粒细胞趋化因子水平明显低于其他组。酶谱技术显示，急性哮喘患者血浆中MMP-9（92 kDa）的活性显著增加，但MMP-2（66 kDa）的活性未增加。
本研究中观察到的MMP-9产生和活性增加表明急性重症哮喘患者存在细胞外基质降解过程，并提示MMP-9可作为哮喘炎症和气道重塑的非侵入性全身标志物。
