Kostamo Katriina, Tervahartiala Taina, Sorsa Timo, Richardson Malcolm, Toskala Elina
Department of Otorhinolaryngology, Helsinki University Central Hospital, Institute of Dentistry, University of Helsinki, Helsinki, Finland.
Laryngoscope. 2007 Apr;117(4):638-43. doi: 10.1097/MLG.0b013e318030aca6.
Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma share characteristic inflammatory features and histopathologic findings of airway remodeling. Remodeling, which is controlled by matrix metalloproteinases (MMP), is a key event in the pathogenesis of asthma. The MMP functions have rarely been evaluated in CRSwNP.
Prospective and in vivo.
MMP-7, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations were analyzed by enzyme-linked immunosorbent assay and their molecular forms by Western immunoblotting and gelatin zymography in 24 patients operated on for CRSwNP and in nasal lavages from 19 healthy controls. MMP function, protective or destructive, was evaluated by comparing MMP/TIMP-1 levels with the disease activity, estimated by tissue eosinophilia and a need for re-operations.
Significantly increased levels of MMP-8/TIMP-1 and MMP-9/TIMP-1 were found in patients without tissue eosinophilia relative to eosinophil-positive CRSwNP patients and controls, as well as in patients who did not require re-operation in comparison with re-operated patients. In eosinophil-positive and re-operated patients, these parameters were within the same range than in controls.
Proteolytic spectrum is different in eosinophilic and noneosinophilic CRSwNP, suggesting a new mechanism for eosinophil accumulation in the disease pathogenesis. Enhanced MMP-8 and MMP-9 expression was associated with a better prognosis/clinical outcome, and thus these results may represent a synergic, protective role of MMP-8 and MMP-9 in host response in CRSwNP. Because synthetic MMP inhibitors, capable of equilibrating the unfavorable MMP/TIMP-ratio, may be of potential therapeutic value in chronic respiratory tract diseases, the MMP functions in inflammatory conditions need to be carefully established.
伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）和哮喘具有气道重塑的特征性炎症特征和组织病理学表现。由基质金属蛋白酶（MMP）控制的重塑是哮喘发病机制中的关键事件。MMP的功能在CRSwNP中很少被评估。
前瞻性和体内研究。
采用酶联免疫吸附测定法分析24例接受CRSwNP手术患者以及19例健康对照者鼻腔灌洗液中MMP-7、MMP-8、MMP-9和金属蛋白酶组织抑制剂（TIMP）-1的浓度，并通过Western免疫印迹和明胶酶谱法分析其分子形式。通过比较MMP/TIMP-1水平与疾病活动度（通过组织嗜酸性粒细胞增多和再次手术需求来评估）来评估MMP的保护或破坏性功能。
相对于嗜酸性粒细胞阳性的CRSwNP患者和对照者，无组织嗜酸性粒细胞的患者以及与再次手术患者相比无需再次手术的患者中，MMP-8/TIMP-1和MMP-9/TIMP-1水平显著升高。在嗜酸性粒细胞阳性和再次手术的患者中，这些参数与对照者处于相同范围。
嗜酸性和非嗜酸性CRSwNP中的蛋白水解谱不同，提示在疾病发病机制中嗜酸性粒细胞积聚的新机制。MMP-8和MMP-9表达增强与较好的预后/临床结果相关，因此这些结果可能代表MMP-8和MMP-9在CRSwNP宿主反应中的协同保护作用。由于能够平衡不利的MMP/TIMP比值的合成MMP抑制剂可能在慢性呼吸道疾病中具有潜在治疗价值，因此需要仔细确定炎症状态下的MMP功能。
