Patchell B J, Dorscheid D R
James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Department of Medicine, University of British Columbia, Vancouver BC, Canada.
Clin Exp Allergy. 2006 May;36(5):585-93. doi: 10.1111/j.1365-2222.2006.02394.x.
The airway epithelium acts as a protective barrier, separating the external environment from the underlying tissue. Daily challenges result in damage to the epithelium that, in normal individuals, is quickly and effectively repaired. In respiratory diseases, such as asthma, this repair is compromised. Following injury to the epithelium, plasma leaks into the airway lumen acting as a protective protein cap. Carbohydrates are mediators of epithelial repair, however, the associated regulatory proteins remain unknown.
To identify mediators of epithelial repair based on their carbohydrate moieties using an in vitro wound repair culture model of human airway epithelial cells (1HAEo(-)).
Using the lectin Allomyrina dichotoma agglutinin (AlloA) as a tool, ligands essential in the repair of damaged epithelium were characterized. AlloA was subsequently used to purify and identify a glycoprotein associated with epithelial repair.
The addition of AlloA to the media of mechanically wounded monolayers inhibited repair. Fetuin, a highly glycosylated serum protein, was identified as a glycoprotein bound by AlloA. The addition of fetuin to serum starved monolayers stimulated wound closure.
These results indicate that following mechanical injury to the epithelium, serum glycoproteins, not only provide a protective barrier, but also are involved in the initiation of wound closure.
气道上皮作为一道保护屏障,将外部环境与下方组织分隔开来。日常刺激会导致上皮受损,在正常个体中,这种损伤会迅速且有效地得到修复。在哮喘等呼吸系统疾病中,这种修复功能会受到损害。上皮损伤后,血浆会渗漏到气道腔内形成一种保护性蛋白帽。碳水化合物是上皮修复的介质,然而,与之相关的调节蛋白仍不清楚。
利用人气道上皮细胞(1HAEo(-))的体外伤口修复培养模型,基于碳水化合物部分鉴定上皮修复的介质。
使用独角仙凝集素(AlloA)作为工具,对受损上皮修复中必需的配体进行表征。随后使用AlloA纯化并鉴定与上皮修复相关的一种糖蛋白。
向机械损伤的单层细胞培养基中添加AlloA会抑制修复。胎球蛋白是一种高度糖基化的血清蛋白,被鉴定为与AlloA结合的糖蛋白。向血清饥饿的单层细胞中添加胎球蛋白会刺激伤口愈合。
这些结果表明,上皮受到机械损伤后,血清糖蛋白不仅提供保护屏障,还参与伤口愈合的启动。