PDF(Pubmed)
Abstract：
BACKGROUND: Fibroblast differentiation to a myofibroblast phenotype is a feature of airway remodeling in asthma. Lung fibroblasts express the integrin receptor α4β7 and fibronectin induces myofibroblast differentiation via this receptor.
OBJECTIVE: To investigate the role of the β7 integrin receptor subunit and α4β7 integrin complex in airway remodeling and airway hyperresponsiveness (AHR) in a murine model of chronic allergen exposure.
METHODS: C57BL/6 wild type (WT) and β7 integrin null mice (β7 -/-) were sensitized (days 1,10) and challenged with ovalbumin (OVA) three times a week for one or 4 weeks. Similar experiments were performed with WT mice in the presence or absence of α4β7 blocking antibodies. Bronchoalveolar (BAL) cell counts, AHR, histological evaluation, soluble collagen content, Transforming growth factor-β (TGFβ) and Interleukin-13 (IL13) were measured. Phenotype of fibroblasts cultured from WT and β7 -/- saline (SAL) and OVA treated mice was evaluated.
RESULTS: Eosinophil numbers were similar in WT vs β7-/- mice. Prolonged OVA exposure in β7-/- mice was associated with reduced AHR, lung collagen content, peribronchial smooth muscle, lung tissue TGFβ and IL13 expression as compared to WT. Similar findings were observed in WT mice treated with α4β7 blocking antibodies. Fibroblast migration was enhanced in response to OVA in WT but not β7 -/- fibroblasts. α-SMA and fibronectin expression were reduced in β7-/- fibroblasts relative to WT.
CONCLUSIONS: The β7 integrin subunit and the α4β7 integrin complex modulate AHR and airway remodeling in a murine model of allergen exposure. This effect is, at least in part, explained by inhibition of fibroblast activation and is independent of eosinophilic inflammation.
OBJECTIVE: To investigate the role of the β7 integrin receptor subunit and α4β7 integrin complex in airway remodeling and airway hyperresponsiveness (AHR) in a murine model of chronic allergen exposure.
METHODS: C57BL/6 wild type (WT) and β7 integrin null mice (β7 -/-) were sensitized (days 1,10) and challenged with ovalbumin (OVA) three times a week for one or 4 weeks. Similar experiments were performed with WT mice in the presence or absence of α4β7 blocking antibodies. Bronchoalveolar (BAL) cell counts, AHR, histological evaluation, soluble collagen content, Transforming growth factor-β (TGFβ) and Interleukin-13 (IL13) were measured. Phenotype of fibroblasts cultured from WT and β7 -/- saline (SAL) and OVA treated mice was evaluated.
RESULTS: Eosinophil numbers were similar in WT vs β7-/- mice. Prolonged OVA exposure in β7-/- mice was associated with reduced AHR, lung collagen content, peribronchial smooth muscle, lung tissue TGFβ and IL13 expression as compared to WT. Similar findings were observed in WT mice treated with α4β7 blocking antibodies. Fibroblast migration was enhanced in response to OVA in WT but not β7 -/- fibroblasts. α-SMA and fibronectin expression were reduced in β7-/- fibroblasts relative to WT.
CONCLUSIONS: The β7 integrin subunit and the α4β7 integrin complex modulate AHR and airway remodeling in a murine model of allergen exposure. This effect is, at least in part, explained by inhibition of fibroblast activation and is independent of eosinophilic inflammation.
摘要：
背景：成纤维细胞分化为肌成纤维细胞表型是哮喘气道重塑的一个特征。肺成纤维细胞表达整联蛋白受体α4β7，纤连蛋白通过该受体诱导肌成纤维细胞分化。
目的：研究β7整合素受体亚基和α4β7整合素复合物在慢性变应原暴露小鼠模型气道重塑和气道高反应性（AHR）中的作用。
方法:将C57BL/6野生型(WT)和β7整合素缺失小鼠(β7-/-)致敏(第1,10天)并用卵清蛋白(OVA)攻击,每周三次,持续1或4周。在存在或不存在α4β7阻断抗体的情况下,用WT小鼠进行类似的实验。支气管肺泡（BAL）细胞计数，AHR,组织学评估，可溶性胶原蛋白含量，测量转化生长因子-β(TGFβ)和白细胞介素-13(IL13)。评价从WT和β7-/-盐水(SAL)和OVA处理的小鼠培养的成纤维细胞的表型。
结果：WT与β7-/-小鼠的嗜酸性粒细胞数量相似。β7-/-小鼠OVA暴露时间延长与AHR降低相关,肺胶原含量，支气管周围平滑肌，与WT相比,肺组织TGFβ和IL13表达。在用α4β7阻断抗体处理的WT小鼠中观察到类似的发现。WT中的成纤维细胞迁移响应于OVA而不是β7-/-成纤维细胞而增强。相对于WT,α-SMA和纤连蛋白表达在β7-/-成纤维细胞中降低。
结论：在变应原暴露的小鼠模型中，β7整合素亚基和α4β7整合素复合物调节AHR和气道重塑。这种效果是，至少在某种程度上,通过抑制成纤维细胞活化来解释，并且独立于嗜酸性粒细胞炎症。
目的：研究β7整合素受体亚基和α4β7整合素复合物在慢性变应原暴露小鼠模型气道重塑和气道高反应性（AHR）中的作用。
方法:将C57BL/6野生型(WT)和β7整合素缺失小鼠(β7-/-)致敏(第1,10天)并用卵清蛋白(OVA)攻击,每周三次,持续1或4周。在存在或不存在α4β7阻断抗体的情况下,用WT小鼠进行类似的实验。支气管肺泡（BAL）细胞计数，AHR,组织学评估，可溶性胶原蛋白含量，测量转化生长因子-β(TGFβ)和白细胞介素-13(IL13)。评价从WT和β7-/-盐水(SAL)和OVA处理的小鼠培养的成纤维细胞的表型。
结果：WT与β7-/-小鼠的嗜酸性粒细胞数量相似。β7-/-小鼠OVA暴露时间延长与AHR降低相关,肺胶原含量，支气管周围平滑肌，与WT相比,肺组织TGFβ和IL13表达。在用α4β7阻断抗体处理的WT小鼠中观察到类似的发现。WT中的成纤维细胞迁移响应于OVA而不是β7-/-成纤维细胞而增强。相对于WT,α-SMA和纤连蛋白表达在β7-/-成纤维细胞中降低。
结论：在变应原暴露的小鼠模型中，β7整合素亚基和α4β7整合素复合物调节AHR和气道重塑。这种效果是，至少在某种程度上,通过抑制成纤维细胞活化来解释，并且独立于嗜酸性粒细胞炎症。
