Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma
Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma
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DOI：
10.1016/s0002-9440(10)63255-5
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发表时间：
2004-12-01
影响因子：
6
通讯作者：
Liu, FT
中科院分区：
文献类型：
--
作者：
Zuberi, RI;Hsu, DK;Liu, FT
半乳糖凝集素-3是β-半乳糖苷结合动物凝集素家族的成员。先前的体外研究已经证明，半乳糖凝集素-3参与了许多活动，然而，这种凝集素在体内的生理和病理过程中的作用仍有待阐明。在此，我们发现，在卵清蛋白（OVA）诱导的哮喘小鼠模型中，1）支气管周围炎性细胞表达大量的半乳糖凝集素-3; 2）与对照小鼠相比，来自OVA激发小鼠的支气管肺泡灌洗液中含有显著更高水平的半乳糖凝集素-3; 3）支气管肺泡灌洗液中的巨噬细胞是含有半乳糖凝集素-3的主要细胞类型。我们通过比较半乳糖凝集素-3缺陷（gal 3（-/-））小鼠和野生型（gal 3（+/+））小鼠来研究半乳糖凝集素-3在过敏性气道反应中的作用。与相似处理的gal 3（+/+）小鼠相比，在气道OVA激发后，OVA致敏的gal 3（-/-）小鼠产生较少的嗜酸性粒细胞和较低的杯状细胞化生。此外，与gal 3（+/+）小鼠相比，OVA致敏的gal 3（-/-）小鼠在气道OVA激发后发生显著更少的气道高反应性。最后，gal 3（-/-）小鼠产生较低的Th 2应答，但较高的Th 1应答，表明半乳糖凝集素-3调节Th 1/Th 2应答。我们的结论是，半乳糖凝集素-3可能在哮喘的发病机制中起重要作用，该凝集素的抑制剂可能被证明对治疗这种疾病有用。
Galectin-3 is a member of a beta-galactoside-binding animal lectin family. Previous in vitro studies have demonstrated that galectin-3 is involved in a number of activities; however, the roles of this lectin in physiological and pathological processes in vivo remain to be elucidated. Herein, we show, in a murine model of ovalbumin (OVA)-induced asthma that 1) peribronchial inflammatory cells expressed large amounts of galectin-3; 2) bronchoalveolar lavage fluid from OVA-challenged mice contained significantly higher levels of galectin-3 compared to control mice; and 3) macrophages in bronchoalveolar lavage fluid were the major cell type that contained galectin-3. We investigated the role of galectin-3 in the allergic airway response by comparing galectin-3-deficient (gal3(-/-)) mice and wild-type (gal3(+/+)) mice. OVA-sensitized gal3(-/-) mice developed fewer eosinophils and lower goblet cell metaplasia, after airway OVA challenge compared to similarly treated gal3(+/+) mice. In addition, the OVA-sensitized gal3(-/-) mice developed significantly less airway hyperresponsiveness after airway OVA challenge compared to gal3(+/+) mice. Finally, gal3(-/-) mice developed a lower Th2 response, but a higher Th1 response, suggesting that galectin-3 regulates the Th1/Th2 response. we conclude that galectin-3 may play an important role in the pathogenesis of asthma and inhibitors of this lectin may prove useful for treatment of this disease.