在慢性鼻窦炎伴鼻息肉和哮喘中的局部和全身蛋白水解反应
2015/04/27
摘要
背景:慢性鼻窦炎伴鼻息肉(CRSwNP)和哮喘经常并存,共有类似的炎症和重塑。重塑已成为哮喘和CRSwNP的病理生理的一个重要概念。它发生在这些疾病发展的早期并相对地抵抗治疗。负责重塑的关键酶是基质金属蛋白酶(MMPs)。在这项研究中,我们探讨哮喘和CRSwNP是否有着相似的MMP概况。
方法:收集2007年12月和2009年5月之间对照(19例)和哮喘患者(12例),CRSwNP患者(39例),或同时患有哮喘和CRSwNP的患者(16例)的鼻腔分泌物和血清样品,每组按照特异反应性分为2个亚组。 MMP-7,MMP-9,MMP-13,金属蛋白酶组织抑制因子(TIMPs),TIMP-1和TIMP-2,髓过氧化物酶(MPO),和人中性粒细胞弹性蛋白酶(HNE)采用酶联免疫吸附法(ELISA )进行测定, MMP-8使用荧光免疫测定法来确定。高敏C反应蛋白(hs-CRP)的测定用于评估系统损伤。
结果:与对照组相比,哮喘,CRSwNP或两者共患者的鼻分泌物中均表现出较低的MMP-9,MMP-9/ TIMP-1,MMP-9/ TIMP-2和MPO水平(CRSwNP患者中 P <0.05);血清中表现出较高的MMP-9,MMP-9 / TIMP-1,MMP-9 / TIMP-2和HNE水平(所有组中P <0.05);而MMP-7,MMP-13,TIMP-1,和TIMP-2在检测中无差异。特异反应性增加了鼻MMP-9和MPO的表达。CRSwNP患者和哮喘患者血清hs-CRP与对照组相比较高。
结论:我们的研究结果表明哮喘和CRSwNP有共享的病理机制。局部与全身结果的对比反映出健康粘膜对外源性刺激作出反应的不同的能力,可能表明MMP-9对呼吸道具有保护功能,MMP-8也可能具有类似功能。
(苏欣 审校)
Int Forum Allergy Rhinol. 2015 Feb 3. doi: 10.1002/alr.21486. [Epub ahead of print]
Local and systemic proteolytic responses in chronic rhinosinusitis with nasal polyposis and asthma.
Katainen E1, Kostamo K, Virkkula P, Sorsa T, Tervahartiala T, Haapaniemi A, Toskala E.
ABSTRACT
BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma coexist frequently and share similar features of inflammation and remodeling. Remodeling has become an important concept in the pathophysiology of asthma and CRSwNP. It happens early in the development of these diseases and is relatively resistant to treatments. The key enzymes responsible for remodeling are matrix metalloproteinases (MMPs). In this study we examined whether asthma and CRSwNP share similar MMP profiles.
METHODS: Nasal secretion and serum specimens of controls (19 subjects) and patients with asthma (12), CRSwNP (39), or both (16) were collected between December 2007 and May 2009. Groups were divided into 2 subgroups according to atopy. MMP-7, MMP-9, MMP-13, tissue inhibitors of metalloproteinases (TIMPs), TIMP-1 and TIMP-2, myeloperoxidase (MPO), and human neutrophil elastase (HNE) were measured using enzyme-linked immunosorbent assay (ELISA), and MMP-8 was determined using immunofluorometric assay. High-sensitivity C-reactive protein (hs-CRP) was measured to estimate systemic involvement.
RESULTS: Patients with asthma, CRSwNP, or both exhibited lower MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and MPO in nasal secretions (p < 0.05 in CRSwNP) and higher MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and HNE in serum (p < 0.05 in all groups) compared to controls, whereas no difference in MMP-7, MMP-13, TIMP-1, and TIMP-2 were detected. Atopy increased nasal MMP-9 and MPO expression. hs-CRP was higher in patients with CRSwNP and asthma compared to controls.
CONCLUSION: Our findings suggest shared pathomechanisms behind asthma and CRSwNP. Contrasting local vs systemic results reflect a different ability of healthy mucosa to react to exogenous stimuli, possibly indicating a protective function of MMP-9 and possibly also MMP-8 in the airways.
Int Forum Allergy Rhinol. 2015 Feb 3. doi: 10.1002/alr.21486. [Epub ahead of print]