Hospital Clínic, Universitat de Barcelona, CIBER de Enfermedades Respiratorias, Spain.
Am J Rhinol Allergy. 2013 May-Jun;27(3):e69-74. doi: 10.2500/ajra.2013.27.3908.
BACKGROUND: Data on the expression and role of matrix metalloproteinases (MMPs) and their tissue inhibitors (tissue inhibitor of metalloproteinases [TIMPs]) in chronic rhinosinusitis with nasal polyps (CRSwNPs) are contradictory, partly because or the use of different techniques of tissue analysis. The aim of this study was to establish a qualitative/semiquantitative method of analysis on the expression of these remodeling markers in different tissue structures and eosinophils in both NPs and nasal mucosa (NM). METHODS: NP tissues were obtained from patients undergoing endoscopic sinus surgery for severe CRSwNPs (n = 33) and NM tissues from patients undergoing nasal corrective surgery (n = 12). MMPs (MMP-1, MMP-2, MMP-7, and MMP-9) and TIMP type 1 (TIMP-1) expression were evaluated by immunohistochemistry in tissue structures (epithelium, glands, vessels, and extracellular matrix [ECM]) and eosinophils. Tissue eosinophilia was also analyzed in NP tissues. RESULTS: MMPs and TIMP-1 expression were found in the epithelium, glands, vessels, and ECM (in both NM and NP) and in eosinophils (only in NP). Significant (p < 0.01) findings were observed in NP compared with NM: increase in MMP-1 in ECM; decrease in MMP-2 in glands, vessels, and epithelium; decrease in MMP-7 in all tissue structures; increase in MMP-9 in ECM and decrease in epithelium and glands; and no differences in TIMP-1. NP tissues showed a clear eosinophilic inflammation compared with NM (p < 0.01). CONCLUSION: These findings suggest that (1) metalloproteases (MMP-1, MMP-2, MMP-7, and MMP-9) may play an important role in the remodeling of NPs and/or in NP formation and (2) a differential analysis of tissue structures and inflammatory cells should be performed when studying remodeling marker expression and regulation in the upper airways.
背景:关于基质金属蛋白酶(MMPs)及其组织抑制剂(金属蛋白酶组织抑制剂[TIMPs])在慢性鼻-鼻窦炎伴鼻息肉(CRSwNPs)中的表达和作用的数据存在争议,部分原因是组织分析技术的不同。本研究旨在建立一种定性/半定量分析方法,以研究这些重塑标志物在鼻息肉(NP)和鼻腔黏膜(NM)不同组织结构和嗜酸性粒细胞中的表达。
方法:从接受内镜鼻窦手术治疗严重 CRSwNPs 的患者(n = 33)中获取 NP 组织,从接受鼻矫正手术的患者(n = 12)中获取 NM 组织。通过免疫组织化学方法评估 MMPs(MMP-1、MMP-2、MMP-7 和 MMP-9)和 TIMP 型 1(TIMP-1)在组织结构(上皮、腺体、血管和细胞外基质[ECM])和嗜酸性粒细胞中的表达。还分析了 NP 组织中的组织嗜酸性粒细胞。
结果:在 NM 和 NP 中均在上皮、腺体、血管和 ECM 中以及嗜酸性粒细胞中发现 MMPs 和 TIMP-1 表达(仅在 NP 中)。与 NM 相比,NP 中存在显著(p < 0.01)的发现:ECM 中 MMP-1 增加;腺体、血管和上皮中 MMP-2 减少;所有组织结构中 MMP-7 减少;ECM 中 MMP-9 增加,上皮和腺体减少;TIMP-1 无差异。与 NM 相比,NP 组织表现出明显的嗜酸性粒细胞炎症(p < 0.01)。
结论:这些发现表明:(1)金属蛋白酶(MMP-1、MMP-2、MMP-7 和 MMP-9)可能在 NP 的重塑和/或 NP 形成中发挥重要作用;(2)在研究上呼吸道重塑标志物的表达和调节时,应对上气道的组织结构和炎症细胞进行差异分析。
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