Adam E C, Holgate S T, Fildew C J, Lackie P M
Respiratory Cell and Molecular Biology Division, University of Southampton, Southampton, UK.
Clin Exp Allergy. 2003 Oct;33(10):1398-404. doi: 10.1046/j.1365-2222.2003.01771.x.
The epithelial layer in the conducting airway provides a primary protective barrier. Repair of this barrier normally occurs rapidly after damage, but is compromised in diseases such as asthma.
We have developed a human in vitro model system to test our hypothesis that cell surface glycoconjugate-based interactions are required for the normal repair of damaged epithelium.
Lectins having narrow carbohydrate specificities were used to identify and block specific carbohydrate moieties on human airway-derived epithelial cells in culture.
The lectin wheat germ agglutinin bound to N-acetyl glucosamine and inhibited the repair of epithelial damage while having little effect on cell viability. In contrast, other N-acetyl glucosamine binding lectins had no effect even when bound to the cell surface. The involvement of glycoconjugates was confirmed by pre-incubating the lectin with its specific sugar, preventing the inhibition of repair.
These results indicate that lectin-binding sites are involved in epithelial repair and may be important in the repetitive cycles of injury and repair seen in asthma. This model system provides an insight into the role of glycoconjugates and will help to determine the function of specific carbohydrate groups in epithelial repair. These may present a target for therapeutic intervention in respiratory and other diseases.
传导气道中的上皮层提供了主要的保护屏障。该屏障受损后通常能迅速修复,但在哮喘等疾病中会受到损害。
我们开发了一种人体体外模型系统,以验证我们的假设,即基于细胞表面糖缀合物的相互作用是受损上皮正常修复所必需的。
使用具有狭窄碳水化合物特异性的凝集素来识别和阻断培养的人气道来源上皮细胞上的特定碳水化合物部分。
凝集素麦胚凝集素与N-乙酰葡糖胺结合,抑制上皮损伤的修复,而对细胞活力影响很小。相比之下,其他与N-乙酰葡糖胺结合的凝集素即使与细胞表面结合也没有效果。通过将凝集素与其特定糖类预孵育,证实了糖缀合物的参与,从而防止了对修复的抑制。
这些结果表明凝集素结合位点参与上皮修复,在哮喘中所见的反复损伤和修复循环中可能很重要。该模型系统有助于深入了解糖缀合物的作用,并将有助于确定特定碳水化合物基团在上皮修复中的功能。这些可能为呼吸系统疾病和其他疾病的治疗干预提供靶点。