Allergen-induced airway remodeling is impaired in galectin-3-deficient mice.
Allergen-induced airway remodeling is impaired in galectin-3-deficient mice.
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DOI：
10.4049/jimmunol.1000039
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发表时间：
2010-07-15
期刊：
影响因子：
--
通讯作者：
Sriramarao P
中科院分区：
文献类型：
--
作者：
Ge XN;Bahaie NS;Kang BN;Hosseinkhani MR;Ha SG;Frenzel EM;Liu FT;Rao SP;Sriramarao P
β-半乳糖苷结合凝集素半乳糖凝集素 3 (Gal-3) 在气道重塑中发挥的作用是哮喘的一个特征，可导致人类气道功能障碍和不良临床结果，在慢性过敏性气道炎症的小鼠模型中进行了研究。野生型 (WT) 和 Gal-3 敲除 (KO) 小鼠接受卵清蛋白 (OVA) 重复过敏原激发长达 12 周，并评估最后一次激发后收集的支气管肺泡灌洗液 (BALF) 和肺组织，评估与气道重塑相关的细胞特征。与WT小鼠相比，Gal-3 KO小鼠的慢性OVA攻击导致气道重塑减弱，粘液分泌、上皮下纤维化、平滑肌厚度和支气管周围血管生成显着减少。 WT 小鼠气道重塑程度较高与 BALF 和肺组织中 Gal-3 表达较高相关。 BALF 和肺免疫组织学中的细胞计数表明，与 WT 小鼠相比，OVA 攻击的 Gal-3 KO 小鼠中的嗜酸性粒细胞浸润显着减少。对与嗜酸性粒细胞募集和气道重塑相关的细胞介质的评估表明，Gal-3 KO 小鼠中嗜酸性粒细胞活化趋化因子-1、IL-5、IL-13、FIZZ1 和 TGF-β 的水平显着降低。最后，与 WT 细胞相比，来自 Gal-3 KO 小鼠的白细胞表现出血管内皮粘附分子的运输（滚动）减少。总体而言，这些研究表明 Gal-3 是一种重要的凝集素，可通过气道募集炎症细胞（特别是嗜酸性粒细胞）、Th2 表型的发展以及嗜酸性粒细胞特异性趋化因子、促纤维生成和血管生成介质的表达增加来促进气道重塑。
The role played by the β-galactoside-binding lectin galectin-3 (Gal-3) in airway remodeling, a characteristic feature of asthma that leads to airway dysfunction and poor clinical outcome in humans, was investigated in a murine model of chronic allergic airway inflammation. Wild-type (WT) and Gal-3 knock-out (KO) mice were subjected to repetitive allergen challenge with ovalbumin (OVA) up to 12 weeks and bronchoalveolar lavage fluid (BALF) and lung tissue collected after the last challenge were evaluated for cellular features associated with airway remodeling. Compared to WT mice, chronic OVA challenge in Gal-3 KO mice resulted in diminished remodeling of the airways with significantly reduced mucus secretion, sub-epithelial fibrosis, smooth muscle thickness, and peribronchial angiogenesis. The higher degree of airway remodeling in WT mice was associated with higher Gal-3 expression in the BALF as well as lung tissue. Cell counts in BALF and lung immunohistology demonstrated that eosinophil infiltration in OVA-challenged Gal-3 KO mice was significantly reduced compared to WT mice. Evaluation of cellular mediators associated with eosinophil recruitment and airway remodeling revealed that levels of eotaxin-1, IL-5, IL-13, FIZZ1 and TGF-β were substantially lower in Gal-3 KO mice. Finally, leukocytes from Gal-3 KO mice demonstrated decreased trafficking (rolling) on vascular endothelial adhesion molecules compared to WT cells. Overall, these studies demonstrate that Gal-3 is an important lectin that promotes airway remodeling via airway recruitment of inflammatory cells, specifically eosinophils, and the development of a Th2 phenotype as well as increased expression of eosinophil-specific chemokines, pro-fibrogenic and angiogenic mediators.
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影响因子：
11.4
作者：
Holcomb, IN;Kabakoff, RC;Hébert, CC
通讯作者：
Hébert, CC
DOI：
10.1084/jem.194.6.809
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee CG;Homer RJ;Zhu Z;Lanone S;Wang X;Koteliansky V;Shipley JM;Gotwals P;Noble P;Chen Q;Senior RM;Elias JA
通讯作者：
Elias JA
影响因子：
2.8
作者：
Alves, Celene M. O. S.;Silva, Deise A. O.;Mineo, Jose R.
通讯作者：
Mineo, Jose R.
影响因子：
1.9
作者：
Dong, Liang;Wang, Shu-Juan;Bi, Wen-Xiang
通讯作者：
Bi, Wen-Xiang
DOI：
10.1073/pnas.0511167103
发表时间：
2006-03-28
影响因子：
11.1
作者：
Henderson, NC;Mackinnon, AC;Sethi, T
通讯作者：
Sethi, T